CN117377689A - 结合cd3和gpc3的异二聚抗体 - Google Patents
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Abstract
本文提供了新型GPC3结合结构域和包含此类GPC3结合结构域的抗体(例如，抗GPC3×抗CD3)。本文还提供了使用此类抗体用于治疗GPC3相关癌症的方法。
Description
优先权声明
本申请要求2021年3月10日提交的美国临时专利申请号63/159,058和2021年4月9日提交的美国临时专利申请号63/173,127的权益，这些美国临时专利申请据此全文以引用方式并入。
序列表
本申请含有序列表，该序列表以ASCII格式以电子方式提交，并且特此以全文引用的方式并入。在2022年2月28日创建的所述ASCII拷贝命名为067461-5282-WO_SL.txt，并且大小为853,417字节。
发明内容
本文提供了新型GPC3结合结构域和包含此类GPC3结合结构域的抗体(例如，抗GPC3×抗CD3)。本文还提供了使用此类抗体用于治疗GPC3相关癌症的方法。
在第一方面，本文提供了一种包含GPC3抗原结合结构域(ABD)的组合物。该GPC3结合结构域包含来自选自由以下组成的组的可变重链结构域(VH)/可变轻链结构域(VL)对的一组6个CDR(vhCDR1、vhCDR2、vhCDR3、vlCDR1、vlCDR2和vlCDR3)：[GPC3]H1_L1、[GPC3]H1_L1.1、[GPC3]H1_L1.2、[GPC3]H1_L1.3、[GPC3]H1_L1.4、[GPC3]H1_L1.5、[GPC3]H1_L1.6、[GPC3]H1_L1.7、[GPC3]H1_L1.8、[GPC3]H1_L1.9、[GPC3]H1_L1.10、[GPC3]H1_L1.16、[GPC3]H1_L1.23、[GPC3]H1_L1.29、[GPC3]H1_L1.31、[GPC3]H1_L1.65、[GPC3]H1_L1.66、[GPC3]H1_L1.67、[GPC3]H1_L1.68、[GPC3]H1_L1.70、[GPC3]H1_L1.71、[GPC3]H1_L1.72、[GPC3]H1_L1.73、[GPC3]H1.1_L1、[GPC3]H1.1_L1.1、[GPC3]H1.1_L1.2、[GPC3]H1.1_L1.3、[GPC3]H1.1_L1.4、[GPC3]H1.1_L1.5、[GPC3]H1.1_L1.6、[GPC3]H1.1_L1.7、[GPC3]H1.1_L1.8、[GPC3]H1.1_L1.9、[GPC3]H1.1_L1.10、[GPC3]H1.1_L1.16、[GPC3]H1.1_L1.23、[GPC3]H1.1_L1.29、[GPC3]H1.1_L1.31、[GPC3]H1.1_L1.65、[GPC3]H1.1_L1.66、L1.67、[GPC3]H1.1_L1.68、[GPC3]H1.1_L1.70、[GPC3]H1.1_L1.71、[GPC3]H1.1_L1.72、[GPC3]H1.1_L1.73、[GPC3]H1.2_L1、[GPC3]H1.2_L1.1、[GPC3]H1.2_L1.2、[GPC3]H1.2_L1.3、[GPC3]H1.2_L1.4、[GPC3]H1.2_L1.5、[GPC3]H1.2_L1.6、[GPC3]H1.2_L1.7、[GPC3]H1.2_L1.8、[GPC3]H1.2_L1.9、[GPC3]H1.2_L1.10、[GPC3]H1.2_L1.16、[GPC3]H1.2_L1.23、[GPC3]H1.2_L1.29、[GPC3]H1.2_L1.31、[GPC3]H1.2_L1.65、[GPC3]H1.2_L1.66、[GPC3]H1.2_L1.67、[GPC3]H1.2_L1.68、[GPC3]H1.2_L1.70、[GPC3]H1.2_L1.71、[GPC3]H1.2_L1.72、[GPC3]H1.2_L1.73、[GPC3]H1.3_L1、[GPC3]H1.3_L1.1、[GPC3]H1.3_L1.2、[GPC3]H1.3_L1.3、[GPC3]H1.3_L1.4、[GPC3]H1.3_L1.5、[GPC3]H1.3_L1.6、[GPC3]H1.3_L1.7、[GPC3]H1.3_L1.8、[GPC3]H1.3_L1.9、[GPC3]H1.3_L1.10、[GPC3]H1.3_L1.16、[GPC3]H1.3_L1.23、[GPC3]H1.3_L1.29、[GPC3]H1.3_L1.31、[GPC3]H1.3_L1.65、[GPC3]H1.3_L1.66、[GPC3]H1.3_L1.67、[GPC3]H1.3_L1.68、[GPC3]H1.3_L1.70、[GPC3]H1.3_L1.71、[GPC3]H1.3_L1.72、[GPC3]H1.3_L1.73、[GPC3]H1.4_L1、[GPC3]H1.4_L1.1、[GPC3]H1.4_L1.2、[GPC3]H1.4_L1.3、[GPC3]H1.4_L1.4、[GPC3]H1.4_L1.5、[GPC3]H1.4_L1.6、[GPC3]H1.4_L1.7、[GPC3]H1.4_L1.8、[GPC3]H1.4_L1.9、[GPC3]H1.4_L1.10、[GPC3]H1.4_L1.16、[GPC3]H1.4_L1.23、[GPC3]H1.4_L1.29、[GPC3]H1.4_L1.31、[GPC3]H1.4_L1.65、[GPC3]H1.4_L1.66、[GPC3]H1.4_L1.67、[GPC3]H1.4_L1.68、[GPC3]H1.4_L1.70、[GPC3]H1.4_L1.71、[GPC3]H1.4_L1.72和[GPC3]H1.4_L1.73。
在一些实施方案中，ABD具有选自由以下组成的组的VH/VL对：[GPC3]H1_L1、[GPC3]H1_L1.1、[GPC3]H1_L1.2、[GPC3]H1_L1.3、[GPC3]H1_L1.4、[GPC3]H1_L1.5、[GPC3]H1_L1.6、[GPC3]H1_L1.7、[GPC3]H1_L1.8、[GPC3]H1_L1.9、[GPC3]H1_L1.10、[GPC3]H1_L1.16、[GPC3]H1_L1.23、[GPC3]H1_L1.29、[GPC3]H1_L1.31、[GPC3]H1_L1.65、[GPC3]H1_L1.66、[GPC3]H1_L1.67、[GPC3]H1_L1.68、[GPC3]H1_L1.70、[GPC3]H1_L1.71、[GPC3]H1_L1.72、[GPC3]H1_L1.73、[GPC3]H1.1_L1、[GPC3]H1.1_L1.1、[GPC3]H1.1_L1.2、[GPC3]H1.1_L1.3、[GPC3]H1.1_L1.4、[GPC3]H1.1_L1.5、[GPC3]H1.1_L1.6、[GPC3]H1.1_L1.7、[GPC3]H1.1_L1.8、[GPC3]H1.1_L1.9、[GPC3]H1.1_L1.10、[GPC3]H1.1_L1.16、[GPC3]H1.1_L1.23、[GPC3]H1.1_L1.29、[GPC3]H1.1_L1.31、[GPC3]H1.1_L1.65、[GPC3]H1.1_L1.66、L1.67、[GPC3]H1.1_L1.68、[GPC3]H1.1_L1.70、[GPC3]H1.1_L1.71、[GPC3]H1.1_L1.72、[GPC3]H1.1_L1.73、[GPC3]H1.2_L1、[GPC3]H1.2_L1.1、[GPC3]H1.2_L1.2、[GPC3]H1.2_L1.3、[GPC3]H1.2_L1.4、[GPC3]H1.2_L1.5、[GPC3]H1.2_L1.6、[GPC3]H1.2_L1.7、[GPC3]H1.2_L1.8、[GPC3]H1.2_L1.9、[GPC3]H1.2_L1.10、[GPC3]H1.2_L1.16、[GPC3]H1.2_L1.23、[GPC3]H1.2_L1.29、[GPC3]H1.2_L1.31、[GPC3]H1.2_L1.65、[GPC3]H1.2_L1.66、[GPC3]H1.2_L1.67、[GPC3]H1.2_L1.68、[GPC3]H1.2_L1.70、[GPC3]H1.2_L1.71、[GPC3]H1.2_L1.72、[GPC3]H1.2_L1.73、[GPC3]H1.3_L1、[GPC3]H1.3_L1.1、[GPC3]H1.3_L1.2、[GPC3]H1.3_L1.3、[GPC3]H1.3_L1.4、[GPC3]H1.3_L1.5、[GPC3]H1.3_L1.6、[GPC3]H1.3_L1.7、[GPC3]H1.3_L1.8、[GPC3]H1.3_L1.9、[GPC3]H1.3_L1.10、[GPC3]H1.3_L1.16、[GPC3]H1.3_L1.23、[GPC3]H1.3_L1.29、[GPC3]H1.3_L1.31、[GPC3]H1.3_L1.65、[GPC3]H1.3_L1.66、[GPC3]H1.3_L1.67、[GPC3]H1.3_L1.68、[GPC3]H1.3_L1.70、[GPC3]H1.3_L1.71、[GPC3]H1.3_L1.72、[GPC3]H1.3_L1.73、[GPC3]H1.4_L1、[GPC3]H1.4_L1.1、[GPC3]H1.4_L1.2、[GPC3]H1.4_L1.3、[GPC3]H1.4_L1.4、[GPC3]H1.4_L1.5、[GPC3]H1.4_L1.6、[GPC3]H1.4_L1.7、[GPC3]H1.4_L1.8、[GPC3]H1.4_L1.9、[GPC3]H1.4_L1.10、[GPC3]H1.4_L1.16、[GPC3]H1.4_L1.23、[GPC3]H1.4_L1.29、[GPC3]H1.4_L1.31、[GPC3]H1.4_L1.65、[GPC3]H1.4_L1.66、[GPC3]H1.4_L1.67、[GPC3]H1.4_L1.68、[GPC3]H1.4_L1.70、[GPC3]H1.4_L1.71、[GPC3]H1.4_L1.72和[GPC3]H1.4_L1.73。
在一些实施方案中，VH/VL对选自由[GPC3]H1.1_L1.16和[GPC3]H1.1_L1.69组成的组。在示例性实施方案中，组合物是单克隆抗体。
在另一方面，本文提供了一种异二聚抗体，该异二聚抗体包含：a)第一单体，b)第二单体，和c)轻链。第一单体包含：i)抗CD3 scFv，该抗CD3scFv包含第一可变轻链结构域、scFv接头和第一可变重链结构域；和ii)第一Fc结构域，其中scFv使用结构域接头共价附接至第一Fc结构域的N末端。第二单体包含VH2-CH1-铰链-CH2-CH3单体，其中VH是第二可变重链结构域，并且CH2-CH3是第二Fc结构域。在此实施方案中，第二可变重链结构域和第二可变轻链结构域形成GPC3抗原结合结构域(ABD)。
在一些实施方案中，GPC3结合结构域包含来自选自由以下组成的组的VH/VL对的一组6个CDR(vhCDR1、vhCDR2、vhCDR3、vlCDR1、vlCDR2和vlCDR3)：[GPC3]H1_L1、[GPC3]H1_L1.1、[GPC3]H1_L1.2、[GPC3]H1_L1.3、[GPC3]H1_L1.4、[GPC3]H1_L1.5、[GPC3]H1_L1.6、[GPC3]H1_L1.7、[GPC3]H1_L1.8、[GPC3]H1_L1.9、[GPC3]H1_L1.10、[GPC3]H1_L1.16、[GPC3]H1_L1.23、[GPC3]H1_L1.29、[GPC3]H1_L1.31、[GPC3]H1_L1.65、[GPC3]H1_L1.66、[GPC3]H1_L1.67、[GPC3]H1_L1.68、[GPC3]H1_L1.70、[GPC3]H1_L1.71、[GPC3]H1_L1.72、[GPC3]H1_L1.73、[GPC3]H1.1_L1、[GPC3]H1.1_L1.1、[GPC3]H1.1_L1.2、[GPC3]H1.1_L1.3、[GPC3]H1.1_L1.4、[GPC3]H1.1_L1.5、[GPC3]H1.1_L1.6、[GPC3]H1.1_L1.7、[GPC3]H1.1_L1.8、[GPC3]H1.1_L1.9、[GPC3]H1.1_L1.10、[GPC3]H1.1_L1.16、[GPC3]H1.1_L1.23、[GPC3]H1.1_L1.29、[GPC3]H1.1_L1.31、[GPC3]H1.1_L1.65、[GPC3]H1.1_L1.66、L1.67、[GPC3]H1.1_L1.68、[GPC3]H1.1_L1.70、[GPC3]H1.1_L1.71、[GPC3]H1.1_L1.72、[GPC3]H1.1_L1.73、[GPC3]H1.2_L1、[GPC3]H1.2_L1.1、[GPC3]H1.2_L1.2、[GPC3]H1.2_L1.3、[GPC3]H1.2_L1.4、[GPC3]H1.2_L1.5、[GPC3]H1.2_L1.6、[GPC3]H1.2_L1.7、[GPC3]H1.2_L1.8、[GPC3]H1.2_L1.9、[GPC3]H1.2_L1.10、[GPC3]H1.2_L1.16、[GPC3]H1.2_L1.23、[GPC3]H1.2_L1.29、[GPC3]H1.2_L1.31、[GPC3]H1.2_L1.65、[GPC3]H1.2_L1.66、[GPC3]H1.2_L1.67、[GPC3]H1.2_L1.68、[GPC3]H1.2_L1.70、[GPC3]H1.2_L1.71、[GPC3]H1.2_L1.72、[GPC3]H1.2_L1.73、[GPC3]H1.3_L1、[GPC3]H1.3_L1.1、[GPC3]H1.3_L1.2、[GPC3]H1.3_L1.3、[GPC3]H1.3_L1.4、[GPC3]H1.3_L1.5、[GPC3]H1.3_L1.6、[GPC3]H1.3_L1.7、[GPC3]H1.3_L1.8、[GPC3]H1.3_L1.9、[GPC3]H1.3_L1.10、[GPC3]H1.3_L1.16、[GPC3]H1.3_L1.23、[GPC3]H1.3_L1.29、[GPC3]H1.3_L1.31、[GPC3]H1.3_L1.65、[GPC3]H1.3_L1.66、[GPC3]H1.3_L1.67、[GPC3]H1.3_L1.68、[GPC3]H1.3_L1.70、[GPC3]H1.3_L1.71、[GPC3]H1.3_L1.72、[GPC3]H1.3_L1.73、[GPC3]H1.4_L1、[GPC3]H1.4_L1.1、[GPC3]H1.4_L1.2、[GPC3]H1.4_L1.3、[GPC3]H1.4_L1.4、[GPC3]H1.4_L1.5、[GPC3]H1.4_L1.6、[GPC3]H1.4_L1.7、[GPC3]H1.4_L1.8、[GPC3]H1.4_L1.9、[GPC3]H1.4_L1.10、[GPC3]H1.4_L1.16、[GPC3]H1.4_L1.23、[GPC3]H1.4_L1.29、[GPC3]H1.4_L1.31、[GPC3]H1.4_L1.65、[GPC3]H1.4_L1.66、[GPC3]H1.4_L1.67、[GPC3]H1.4_L1.68、[GPC3]H1.4_L1.70、[GPC3]H1.4_L1.71、[GPC3]H1.4_L1.72和[GPC3]H1.4_L1.73。
在示例性实施方案中，GPC3结合结构域包含选自由以下组成的组的VH/VL对：[GPC3]H1_L1、[GPC3]H1_L1.1、[GPC3]H1_L1.2、[GPC3]H1_L1.3、[GPC3]H1_L1.4、[GPC3]H1_L1.5、[GPC3]H1_L1.6、[GPC3]H1_L1.7、[GPC3]H1_L1.8、[GPC3]H1_L1.9、[GPC3]H1_L1.10、[GPC3]H1_L1.16、[GPC3]H1_L1.23、[GPC3]H1_L1.29、[GPC3]H1_L1.31、[GPC3]H1_L1.65、[GPC3]H1_L1.66、[GPC3]H1_L1.67、[GPC3]H1_L1.68、[GPC3]H1_L1.70、[GPC3]H1_L1.71、[GPC3]H1_L1.72、[GPC3]H1_L1.73、[GPC3]H1.1_L1、[GPC3]H1.1_L1.1、[GPC3]H1.1_L1.2、[GPC3]H1.1_L1.3、[GPC3]H1.1_L1.4、[GPC3]H1.1_L1.5、[GPC3]H1.1_L1.6、[GPC3]H1.1_L1.7、[GPC3]H1.1_L1.8、[GPC3]H1.1_L1.9、[GPC3]H1.1_L1.10、[GPC3]H1.1_L1.16、[GPC3]H1.1_L1.23、[GPC3]H1.1_L1.29、[GPC3]H1.1_L1.31、[GPC3]H1.1_L1.65、[GPC3]H1.1_L1.66、L1.67、[GPC3]H1.1_L1.68、[GPC3]H1.1_L1.70、[GPC3]H1.1_L1.71、[GPC3]H1.1_L1.72、[GPC3]H1.1_L1.73、[GPC3]H1.2_L1、[GPC3]H1.2_L1.1、[GPC3]H1.2_L1.2、[GPC3]H1.2_L1.3、[GPC3]H1.2_L1.4、[GPC3]H1.2_L1.5、[GPC3]H1.2_L1.6、[GPC3]H1.2_L1.7、[GPC3]H1.2_L1.8、[GPC3]H1.2_L1.9、[GPC3]H1.2_L1.10、[GPC3]H1.2_L1.16、[GPC3]H1.2_L1.23、[GPC3]H1.2_L1.29、[GPC3]H1.2_L1.31、[GPC3]H1.2_L1.65、[GPC3]H1.2_L1.66、[GPC3]H1.2_L1.67、[GPC3]H1.2_L1.68、[GPC3]H1.2_L1.70、[GPC3]H1.2_L1.71、[GPC3]H1.2_L1.72、[GPC3]H1.2_L1.73、[GPC3]H1.3_L1、[GPC3]H1.3_L1.1、[GPC3]H1.3_L1.2、[GPC3]H1.3_L1.3、[GPC3]H1.3_L1.4、[GPC3]H1.3_L1.5、[GPC3]H1.3_L1.6、[GPC3]H1.3_L1.7、[GPC3]H1.3_L1.8、[GPC3]H1.3_L1.9、[GPC3]H1.3_L1.10、[GPC3]H1.3_L1.16、[GPC3]H1.3_L1.23、[GPC3]H1.3_L1.29、[GPC3]H1.3_L1.31、[GPC3]H1.3_L1.65、[GPC3]H1.3_L1.66、[GPC3]H1.3_L1.67、[GPC3]H1.3_L1.68、[GPC3]H1.3_L1.70、[GPC3]H1.3_L1.71、[GPC3]H1.3_L1.72、[GPC3]H1.3_L1.73、[GPC3]H1.4_L1、[GPC3]H1.4_L1.1、[GPC3]H1.4_L1.2、[GPC3]H1.4_L1.3、[GPC3]H1.4_L1.4、[GPC3]H1.4_L1.5、[GPC3]H1.4_L1.6、[GPC3]H1.4_L1.7、[GPC3]H1.4_L1.8、[GPC3]H1.4_L1.9、[GPC3]H1.4_L1.10、[GPC3]H1.4_L1.16、[GPC3]H1.4_L1.23、[GPC3]H1.4_L1.29、[GPC3]H1.4_L1.31、[GPC3]H1.4_L1.65、[GPC3]H1.4_L1.66、[GPC3]H1.4_L1.67、[GPC3]H1.4_L1.68、[GPC3]H1.4_L1.70、[GPC3]H1.4_L1.71、[GPC3]H1.4_L1.72和[GPC3]H1.4_L1.73。
在示例性实施方案中，GPC3结合结构域包含选自由以下组成的组的VH/VL对：[GPC3]H1.1_L1.16和[GPC3]H1.1_L1.69。
在一些实施方案中，抗CD3 scFv包含选自由以下组成的组的VH和VL对：H1.30_L1.47、H1.32_L1.47、H1.89_L1.47、H1.90_L1.47、H1.33_L1.47、H1.31_L1.47、L1.47_H1.30、L1.47_H1.30、L1.47_H1.32、L1.47_H1.89、L1.47_H1.90、L1.47_H1.33和L1.47_H1.31。
在异二聚抗体的一些实施方案中，scFv接头是带电荷的scFv接头。
在一些实施方案中，第一Fc结构域和第二Fc结构域是变体Fc结构域。在一些实施方案中，第一Fc结构域和第二Fc结构域包含选自由图1A至图1E中所描绘的异二聚化变体组成的组的一组异二聚化变体。在一些实施方案中，组异二聚化变体选自由以下组成的组：S364K/E357Q:L368D/K370S；S364K:L368D/K370S；S364K:L368E/K370S；D401K:T411E/K360E/Q362E；和T366W:T366S/L368A/Y407V，其中编号是根据EU编号进行的。
在一些实施方案中，第一单体和第二单体还包含一种或多种消融变体。在一些实施方案中，一种或多种消融变体是E233P/L234V/L235A/G236del/S267K，其中编号是根据EU编号进行的。
在示例性实施方案中，第一单体或第二单体中的一者包含一种或多种pI变体。在一些实施方案中，一种或多种pI变体是N208D/Q295E/N384D/Q418E/N421D，其中编号是根据EU编号进行的。
在异二聚抗体的示例性实施方案中，第一单体包含氨基酸变体S364K/E357Q/E233P/L234V/L235A/G236del/S267K，第二单体包含氨基酸变体L368D/K370S/N208D/Q295E/N384D/Q418E/N421D/E233P/L234V/L235A/G236del/S267K，并且其中编号是根据EU编号进行的。
在一些实施方案中，第一单体和第二单体各自还包含氨基酸变体428/434S，其中编号是根据EU编号进行的。
在另一方面，本文提供了一种异二聚抗体，该异二聚抗体包含：a)第一单体，该第一单体从N末端到C末端包含scFv-接头-CH2-CH3，其中scFv是抗CD3 scFv，并且CH2-CH3是第一Fc结构域；b)第二单体，该第二单体从N末端到C末端包含VH-CH1-铰链-CH2-CH3，其中CH2-CH3是第二Fc结构域；和c)轻链，该轻链包含VL-CL。第一变体Fc结构域包含氨基酸变体S364K/E357Q，第二变体Fc结构域包含氨基酸变体L368D/K370S，第一变体Fc结构域和第二变体Fc结构域各自包含氨基酸变体E233P/L234V/L235A/G236del/S267K，并且第二单体的CH1-铰链-CH2-CH3包含氨基酸变体N208D/Q295E/N384D/Q418E/N421D(EU编号)。此外，VH和VL形成分别包含选自[GPC3]H1.1_L1.16的GPC3结合结构域的可变重链结构域和[GPC3]H1.1_L1.69的GPC3结合结构域的可变轻链结构域；并且抗CD3 scFv包含选自以下的CD3结合结构域的可变重链结构域和可变轻链结构域：H1.30_L1.47、H1.32_L1.47、H1.89_L1.47、H1.90_L1.47、H1.33_L1.47、H1.31_L1.47、L1.47_H1.30、L1.47_H1.30、L1.47_H1.32、L1.47_H1.89、L1.47_H1.90、L1.47_H1.33和L1.47_H1.31。
在一些实施方案中，第一变体Fc结构域和第二变体Fc结构域各自进一步包含氨基酸变体428/434S，其中编号是根据EU编号进行的。
在另一方面，本文提供了一种异二聚抗体，该异二聚抗体包含：a)第一单体，b)第二单体，和c)共同轻链。第一单体从N末端到C末端包含VH1-CH1-接头1-scFv-接头2-CH2-CH3，其中VH1是第一可变重链结构域，scFv是抗CD3 scFv，接头1和接头2分别是第一结构域接头和第二结构域接头，并且CH2-CH3是第一Fc结构域。第二单体从N末端到C末端包含VH2-CH1-铰链-CH2-CH3，其中VH2是第二可变重链结构域，并且CH2-CH3是第二Fc结构域；和c)共同轻链，该共同轻链包含可变轻链结构域。第一可变重链结构域和可变轻链结构域形成第一CLDN6 ABD，并且第二可变重链结构域和可变轻链结构域形成第二CLDN6 ABD。
在另一方面，本文提供了一种异二聚抗体，该异二聚抗体包含：a)第一单体，b)第二单体，和c)共同轻链。第一单体从N末端到C末端包含VH1-CH1-接头1-scFv-接头2-CH2-CH3，其中VH1是第一可变重链结构域，scFv是抗CD3 scFv，接头1和接头2分别是第一结构域接头和第二结构域接头，并且CH2-CH3是第一Fc结构域。第二单体从N末端到C末端包含VH2-CH1-铰链-CH2-CH3，其中VH2是第二可变重链结构域，并且CH2-CH3是第二Fc结构域；和c)共同轻链，该共同轻链包含可变轻链结构域。第一可变重链结构域和可变轻链结构域形成第一GPC3 ABD，并且第二可变重链结构域和可变轻链结构域形成第二GPC3 ABD。
在一些实施方案中，第一GPC3结合结构域和第二GPC3结合结构域各自包含来自选自由以下组成的组的VH/VL对的一组6个CDR(vhCDR1、vhCDR2、vhCDR3、vlCDR1、vlCDR2和vlCDR3)：[GPC3]H1_L1、[GPC3]H1_L1.1、[GPC3]H1_L1.2、[GPC3]H1_L1.3、[GPC3]H1_L1.4、[GPC3]H1_L1.5、[GPC3]H1_L1.6、[GPC3]H1_L1.7、[GPC3]H1_L1.8、[GPC3]H1_L1.9、[GPC3]H1_L1.10、[GPC3]H1_L1.16、[GPC3]H1_L1.23、[GPC3]H1_L1.29、[GPC3]H1_L1.31、[GPC3]H1_L1.65、[GPC3]H1_L1.66、[GPC3]H1_L1.67、[GPC3]H1_L1.68、[GPC3]H1_L1.70、[GPC3]H1_L1.71、[GPC3]H1_L1.72、[GPC3]H1_L1.73、[GPC3]H1.1_L1、[GPC3]H1.1_L1.1、[GPC3]H1.1_L1.2、[GPC3]H1.1_L1.3、[GPC3]H1.1_L1.4、[GPC3]H1.1_L1.5、[GPC3]H1.1_L1.6、[GPC3]H1.1_L1.7、[GPC3]H1.1_L1.8、[GPC3]H1.1_L1.9、[GPC3]H1.1_L1.10、[GPC3]H1.1_L1.16、[GPC3]H1.1_L1.23、[GPC3]H1.1_L1.29、[GPC3]H1.1_L1.31、[GPC3]H1.1_L1.65、[GPC3]H1.1_L1.66、L1.67、[GPC3]H1.1_L1.68、[GPC3]H1.1_L1.70、[GPC3]H1.1_L1.71、[GPC3]H1.1_L1.72、[GPC3]H1.1_L1.73、[GPC3]H1.2_L1、[GPC3]H1.2_L1.1、[GPC3]H1.2_L1.2、[GPC3]H1.2_L1.3、[GPC3]H1.2_L1.4、[GPC3]H1.2_L1.5、[GPC3]H1.2_L1.6、[GPC3]H1.2_L1.7、[GPC3]H1.2_L1.8、[GPC3]H1.2_L1.9、[GPC3]H1.2_L1.10、[GPC3]H1.2_L1.16、[GPC3]H1.2_L1.23、[GPC3]H1.2_L1.29、[GPC3]H1.2_L1.31、[GPC3]H1.2_L1.65、[GPC3]H1.2_L1.66、[GPC3]H1.2_L1.67、[GPC3]H1.2_L1.68、[GPC3]H1.2_L1.70、[GPC3]H1.2_L1.71、[GPC3]H1.2_L1.72、[GPC3]H1.2_L1.73、[GPC3]H1.3_L1、[GPC3]H1.3_L1.1、[GPC3]H1.3_L1.2、[GPC3]H1.3_L1.3、[GPC3]H1.3_L1.4、[GPC3]H1.3_L1.5、[GPC3]H1.3_L1.6、[GPC3]H1.3_L1.7、[GPC3]H1.3_L1.8、[GPC3]H1.3_L1.9、[GPC3]H1.3_L1.10、[GPC3]H1.3_L1.16、[GPC3]H1.3_L1.23、[GPC3]H1.3_L1.29、[GPC3]H1.3_L1.31、[GPC3]H1.3_L1.65、[GPC3]H1.3_L1.66、[GPC3]H1.3_L1.67、[GPC3]H1.3_L1.68、[GPC3]H1.3_L1.70、[GPC3]H1.3_L1.71、[GPC3]H1.3_L1.72、[GPC3]H1.3_L1.73、[GPC3]H1.4_L1、[GPC3]H1.4_L1.1、[GPC3]H1.4_L1.2、[GPC3]H1.4_L1.3、[GPC3]H1.4_L1.4、[GPC3]H1.4_L1.5、[GPC3]H1.4_L1.6、[GPC3]H1.4_L1.7、[GPC3]H1.4_L1.8、[GPC3]H1.4_L1.9、[GPC3]H1.4_L1.10、[GPC3]H1.4_L1.16、[GPC3]H1.4_L1.23、[GPC3]H1.4_L1.29、[GPC3]H1.4_L1.31、[GPC3]H1.4_L1.65、[GPC3]H1.4_L1.66、[GPC3]H1.4_L1.67、[GPC3]H1.4_L1.68、[GPC3]H1.4_L1.70、[GPC3]H1.4_L1.71、[GPC3]H1.4_L1.72和[GPC3]H1.4_L1.73。
在一些实施方案中，第一GPC3结合结构域和第二GPC3结合结构域中的每一者具有选自由以下组成的组的VH/VL对：[GPC3]H1_L1、[GPC3]H1_L1.1、[GPC3]H1_L1.2、[GPC3]H1_L1.3、[GPC3]H1_L1.4、[GPC3]H1_L1.5、[GPC3]H1_L1.6、[GPC3]H1_L1.7、[GPC3]H1_L1.8、[GPC3]H1_L1.9、[GPC3]H1_L1.10、[GPC3]H1_L1.16、[GPC3]H1_L1.23、[GPC3]H1_L1.29、[GPC3]H1_L1.31、[GPC3]H1_L1.65、[GPC3]H1_L1.66、[GPC3]H1_L1.67、[GPC3]H1_L1.68、[GPC3]H1_L1.70、[GPC3]H1_L1.71、[GPC3]H1_L1.72、[GPC3]H1_L1.73、[GPC3]H1.1_L1、[GPC3]H1.1_L1.1、[GPC3]H1.1_L1.2、[GPC3]H1.1_L1.3、[GPC3]H1.1_L1.4、[GPC3]H1.1_L1.5、[GPC3]H1.1_L1.6、[GPC3]H1.1_L1.7、[GPC3]H1.1_L1.8、[GPC3]H1.1_L1.9、[GPC3]H1.1_L1.10、[GPC3]H1.1_L1.16、[GPC3]H1.1_L1.23、[GPC3]H1.1_L1.29、[GPC3]H1.1_L1.31、[GPC3]H1.1_L1.65、[GPC3]H1.1_L1.66、L1.67、[GPC3]H1.1_L1.68、[GPC3]H1.1_L1.70、[GPC3]H1.1_L1.71、[GPC3]H1.1_L1.72、[GPC3]H1.1_L1.73、[GPC3]H1.2_L1、[GPC3]H1.2_L1.1、[GPC3]H1.2_L1.2、[GPC3]H1.2_L1.3、[GPC3]H1.2_L1.4、[GPC3]H1.2_L1.5、[GPC3]H1.2_L1.6、[GPC3]H1.2_L1.7、[GPC3]H1.2_L1.8、[GPC3]H1.2_L1.9、[GPC3]H1.2_L1.10、[GPC3]H1.2_L1.16、[GPC3]H1.2_L1.23、[GPC3]H1.2_L1.29、[GPC3]H1.2_L1.31、[GPC3]H1.2_L1.65、[GPC3]H1.2_L1.66、[GPC3]H1.2_L1.67、[GPC3]H1.2_L1.68、[GPC3]H1.2_L1.70、[GPC3]H1.2_L1.71、[GPC3]H1.2_L1.72、[GPC3]H1.2_L1.73、[GPC3]H1.3_L1、[GPC3]H1.3_L1.1、[GPC3]H1.3_L1.2、[GPC3]H1.3_L1.3、[GPC3]H1.3_L1.4、[GPC3]H1.3_L1.5、[GPC3]H1.3_L1.6、[GPC3]H1.3_L1.7、[GPC3]H1.3_L1.8、[GPC3]H1.3_L1.9、[GPC3]H1.3_L1.10、[GPC3]H1.3_L1.16、[GPC3]H1.3_L1.23、[GPC3]H1.3_L1.29、[GPC3]H1.3_L1.31、[GPC3]H1.3_L1.65、[GPC3]H1.3_L1.66、[GPC3]H1.3_L1.67、[GPC3]H1.3_L1.68、[GPC3]H1.3_L1.70、[GPC3]H1.3_L1.71、[GPC3]H1.3_L1.72、[GPC3]H1.3_L1.73、[GPC3]H1.4_L1、[GPC3]H1.4_L1.1、[GPC3]H1.4_L1.2、[GPC3]H1.4_L1.3、[GPC3]H1.4_L1.4、[GPC3]H1.4_L1.5、[GPC3]H1.4_L1.6、[GPC3]H1.4_L1.7、[GPC3]H1.4_L1.8、[GPC3]H1.4_L1.9、[GPC3]H1.4_L1.10、[GPC3]H1.4_L1.16、[GPC3]H1.4_L1.23、[GPC3]H1.4_L1.29、[GPC3]H1.4_L1.31、[GPC3]H1.4_L1.65、[GPC3]H1.4_L1.66、[GPC3]H1.4_L1.67、[GPC3]H1.4_L1.68、[GPC3]H1.4_L1.70、[GPC3]H1.4_L1.71、[GPC3]H1.4_L1.72和[GPC3]H1.4_L1.73。在一些实施方案中，VH/VL对选自由[GPC3]H1.1_L1.16和[GPC3]H1.1_L1.69组成的组。
在一些实施方案中，scFv包含具有来自选自由以下组成的组的VH/VL对的一组6个CDR(vhCDR1、vhCDR2、vhCDR3、vlCDR1、vlCDR2和vlCDR3)：H1.30_L1.47、H1.32_L1.47、H1.89_L1.47、H1.90_L1.47、H1.33_L1.47、H1.31_L1.47、L1.47_H1.30、L1.47_H1.30、L1.47_H1.32、L1.47_H1.89、L1.47_H1.90、L1.47_H1.33和L1.47_H1.31。在一些实施方案中，scFv包含以下CD3结合结构域中的任一者的可变重链结构域和可变轻链结构域：H1.30_L1.47、H1.32_L1.47、H1.89_L1.47、H1.90_L1.47、H1.33_L1.47、H1.31_L1.47、L1.47_H1.30、L1.47_H1.30、L1.47_H1.32、L1.47_H1.89、L1.47_H1.90、L1.47_H1.33和L1.47_H1.31。
在异二聚抗体的一些实施方案中，scFv接头是带电荷的scFv接头。在一些实施方案中，scFv接头是具有氨基酸序列(GKPGS)4(SEQ ID NO:1)的带电荷scFv接头。
在一些实施方案中，第一Fc结构域和第二Fc结构域是变体Fc结构域。在一些实施方案中，第一Fc结构域和第二Fc结构域包含选自由图1A至图1E中所描绘的异二聚化变体组成的组的一组异二聚化变体。在一些实施方案中，组异二聚化变体选自由以下组成的组：S364K/E357Q:L368D/K370S；S364K:L368D/K370S；S364K:L368E/K370S；D401K:T411E/K360E/Q362E；和T366W:T366S/L368A/Y407V，其中编号是根据EU编号进行的。
在一些实施方案中，述第一单体和第二单体还包含一种或多种消融变体。在一些实施方案中，一种或多种消融变体是E233P/L234V/L235A/G236del/S267K，其中编号是根据EU编号进行的。
在示例性实施方案中，第一单体或第二单体中的一者包含一种或多种pI变体。在一些实施方案中，一种或多种pI变体是N208D/Q295E/N384D/Q418E/N421D，其中编号是根据EU编号进行的。
在异二聚抗体的示例性实施方案中，第一单体包含氨基酸变体S364K/E357Q/E233P/L234V/L235A/G236del/S267K，第二单体包含氨基酸变体L368D/K370S/N208D/Q295E/N384D/Q418E/N421D/E233P/L234V/L235A/G236del/S267K，并且其中编号是根据EU编号进行的。
在一些实施方案中，第一单体和第二单体各自还包含氨基酸变体428/434S，其中编号是根据EU编号进行的。
45.根据权利要求44所述的异二聚抗体，其中第一变体Fc结构域和第二变体Fc结构域各自还包含氨基酸变体428/434S，其中编号是根据EU编号进行的。
在另一方面，本文提供了异二聚抗体，该异二聚抗体包含：a)第一单体，b)第二单体，和c)共同轻链。第一单体从N末端到C末端包含VH1-CH1-接头1-scFv-接头2-CH2-CH3，其中scFv是抗CD3 scFv，并且CH2-CH3是第一Fc结构域。第二单体从N末端到C末端包含VH1-CH1-铰链-CH2-CH3，其中CH2-CH3是第二Fc结构域。共同轻链包含VL-CL。第一变体Fc结构域包含氨基酸变体S364K/E357Q，第二变体Fc结构域包含氨基酸变体L368D/K370S，第一变体Fc结构域和第二变体Fc结构域各自包含氨基酸变体E233P/L234V/L235A/G236del/S267K，并且第二单体的CH1-铰链-CH2-CH3包含氨基酸变体N208D/Q295E/N384D/Q418E/N421D(EU编号)。VH和VL包含选自以下的GPC3 ABD的可变重链结构域和可变轻链结构域：H1.9_L1.187、H1.24_L1.187、H2.91_L1.187和H1.9_L1.187；并且抗CD3scFv包含选自以下的CD3结合结构域的可变重链结构域和可变轻链结构域：H1.30_L1.47、H1.32_L1.47、H1.89_L1.47、H1.90_L1.47、H1.33_L1.47、H1.31_L1.47、L1.47_H1.30、L1.47_H1.30、L1.47_H1.32、L1.47_H1.89、L1.47_H1.90、L1.47_H1.33和L1.47_H1.31。在一些实施方案中，第一变体Fc结构域和第二变体Fc结构域各自还包含氨基酸变体428/434S。
本文还提供了包含编码本文所述抗体的核酸的核酸组合物、包含此类核酸的表达载体组合物、用于制备包含表达载体组合物的抗体的宿主细胞以及制备抗体的方法。
背景技术
基于抗体的治疗剂已经成功地用于治疗各种疾病，包含癌症。正在探索的日益普遍的途径是共接合两种不同抗原的单一免疫球蛋白分子的工程化。接合两种不同抗原的此类替代性抗体形式通常称为双特异性抗体。因为抗体可变区(Fv)的相当大的多样性使得可以产生识别几乎任何分子的Fv，所以产生双特异性抗体的典型方法是将新的可变区引入到抗体中。
双特异性抗体的特别有用的方法是使接合CD3的第一结合结构域和接合与癌细胞相关或在癌细胞上上调的抗原的第二结合结构域工程化，使得双特异性抗体重定向CD3+T细胞以破坏癌细胞。硫酸乙酰肝素蛋白多糖家族成员磷脂酰肌醇蛋白聚糖3(GPC3)先前已报道在肝细胞癌(特别是肝癌)中高表达，并且在健康组织中最低表达。有鉴于此，据信抗GPC3抗体可用于例如将抗肿瘤治疗剂(例如，化学治疗剂和T细胞)定位至此类表达GPC3的肿瘤。先前靶向GPC3(诸如CD3双特异性抗体)和CAR-T疗法的尝试已经显示出一些成功，但在临床前或临床环境中已经显示不良事件，诸如细胞因子释放综合征。本发明提供了能够将CD3+效应T细胞定位至表达GPC3的肿瘤的具有改善的治疗特性的针对CD3和GPC3的新型双特异性抗体。
附图说明
图1A至图1E描绘了导致Fc异二聚化的Fc异二聚化变体组的有用对(包括偏斜变体和pI变体)。存在并无对应“单体2”变体的变体；这些是可以在任一单体上单独使用的pI变体。
图2描绘了同配变体抗体恒定区和其相应取代的列表。pI_(-)指示较低pI变体，而pI_(+)指示较高pI变体。这些可以任选地且独立地与本发明的其他异二聚化变体(以及其他变体类型，如本文所概述的)组合。
图3描绘有用的消融变体，该有用的消融变体消融FcγR结合(有时被称为“敲除”变体或“KO”变体)。通常，消融变体在两个单体上都可以发现，但是在一些情况下，该消融变体可以仅在一个单体上。
图4描绘了本发明的“非Fv”组分的特别有用的实施方案。
图5描绘了用于增大或减小利用一个或多个scFv作为组分的本发明异源二聚bsAb的pI的如本文所述的多个带电荷的scFv接头。(+H)阳性接头在本文中特别适用，尤其是与本文所示的抗CD3 VL和VH序列一起使用。根据Whitlow等人,《蛋白质工程(ProteinEngineering)》6(8):989-995(1993)，具有单个电荷的单个现有技术scFv接头被称为“Whitlow”。应注意的是，这种接头用于减少scFv中的聚集和增强scFv中的蛋白水解稳定性。此类带电荷的scFv接头可以用于本文公开的本发明抗体形式中的任何本发明抗体形式中，所述本发明抗体形式包含scFv(例如，1+1 Fab-scFv-Fc形式和2+1 Fab2-scFv-Fc形式)。
图6描绘了许多示例性结构域接头。在一些实施方案中，这些接头用于将单链Fv连接到Fc链。在一些实施方案中，这些接头可以组合。例如，GGGGS接头(SEQ ID NO:2)可以与“半铰链”接头组合。
图7A至图7D描绘了基于人IgG1的若干有用的1+1 Fab-scFv-Fc双特异性抗体形式重链主链的序列，没有Fv序列(例如，Fab侧的scFv和VH)。主链1基于人IgG1(356E/358M同种异型)，并且包括S364K/E357Q:L368D/K370S偏斜变体、具有S364K/E357Q偏斜变体的链上的C220S、具有L368D/K370S偏斜变体的链上的N208D/Q295E/N384D/Q418E/N421D pI变体、以及两条链上的E233P/L234V/L235A/G236del/S267K消融变体。主链2基于人IgG1(356E/358M同种异型)，并且包括S364K:L368D/K370S偏斜变体、具有S364K偏斜变体的链上的C220S、具有L368D/K370S偏斜变体的链上的N208D/Q295E/N384D/Q418E/N421D pI变体、以及两条链上的E233P/L234V/L235A/G236del/S267K消融变体。主链3基于人IgG1(356E/358M同种异型)，并且包括S364K:L368E/K370S偏斜变体、具有S364K偏斜变体的链上的C220S、具有L368E/K370S偏斜变体的链上的N208D/Q295E/N384D/Q418E/N421D pI变体、以及两条链上的E233P/L234V/L235A/G236del/S267K消融变体。主链4基于人IgG1(356E/358M同种异型)，并且包括D401K:K360E/Q362E/T411E偏斜变体、具有D401K偏斜变体的链上的C220S、具有K360E/Q362E/T411E偏斜变体的链上的N208D/Q295E/N384D/Q418E/N421D pI变体、以及两条链上的E233P/L234V/L235A/G236del/S267K消融变体。主链5基于人IgG1(356D/358L同种异型)，并且包括S364K/E357Q:L368D/K370S偏斜变体、具有S364K/E357Q偏斜变体的链上的C220S、具有L368D/K370S偏斜变体的链上的N208D/Q295E/N384D/Q418E/N421D pI变体、以及两条链上的E233P/L234V/L235A/G236del/S267K消融变体。主链6基于人IgG1(356E/358M同种异型)，并且包含S364K/E357Q:L368D/K370S偏斜变体、具有S364K/E357Q偏斜变体的链上的C220S、具有L368D/K370S偏斜变体的链上的N208D/Q295E/N384D/Q418E/N421D pI变体、和两条链上的E233P/L234V/L235A/G236del/S267K消融变体，以及两条链上的N297A变体。除了突变是N297S之外，主链7与主链6相同。主链8基于人IgG4，并且包括S364K/E357Q:L368D/K370S偏斜变体、具有L368D/K370S偏斜变体的链上的N208D/Q295E/N384D/Q418E/N421D pI变体、以及两条链上的S228P(EU编号，这是Kabat中的S241P)变体，所述变体消融如本领域已知的Fab臂交换。主链9基于人IgG2，并且包括S364K/E357Q:L368D/K370S偏斜变体、具有L368D/K370S偏斜变体的链上的N208D/Q295E/N384D/Q418E/N421D pI变体。主链10基于人IgG2，并且包括S364K/E357Q:L368D/K370S偏斜变体、具有L368D/K370S偏斜变体的链上的N208D/Q295E/N384D/Q418E/N421D pI变体、以及两条链上的S267K变体。除了主链11包含M428L/N434S Xtend突变之外，主链11与主链1相同。主链12基于人IgG1(356E/358M同种异型)，并且包含S364K/E357Q:L368D/K370S偏斜变体、具有S364K/E357Q偏斜变体的链上的C220S和P217R/P229R/N276K pI变体，以及两条链上的E233P/L234V/L235A/G236del/S267K消融变体。在这些主链的每一条主链内包括与所列举的序列90％、95％、98％和99％相同(如本文所定义)和/或含有1个、2个、3个、4个、5个、6个、7个、8个、9个或10个另外的氨基酸取代的序列(与附图的“亲本”相比，如本领域技术人员将理解，与亲本人IgG1(或IgG2或IgG4，这取决于主链)相比，已经含有多个氨基酸修饰)。即，除了此图的主链中所含的偏斜变体、pI变体和消融变体之外，所列举主链可以含有另外的氨基酸修饰(通常是氨基酸取代)。
图8A至图8C描绘了基于人IgG1的若干有用的2+1 Fab2-scFv-Fc双特异性抗体形式重链主链的序列，没有Fv序列(例如，Fab侧的scFv和VH)。主链1基于人IgG1(356E/358M同种异型)，并且包含S364K/E357Q:L368D/K370S偏斜变体、具有L368D/K370S偏斜变体的链上的N208D/Q295E/N384D/Q418E/N421D pI变体、以及两条链上的E233P/L234V/L235A/G236del/S267K消融变体。主链2基于人IgG1(356E/358M同种异型)，并且包含S364K:L368D/K370S偏斜变体、具有L368D/K370S偏斜变体的链上的N208D/Q295E/N384D/Q418E/N421D pI变体、以及两条链上的E233P/L234V/L235A/G236del/S267K消融变体。主链3基于人IgG1(356E/358M同种异型)，并且包含S364K:L368E/K370S偏斜变体、具有L368E/K370S偏斜变体的链上的N208D/Q295E/N384D/Q418E/N421D pI变体、以及两条链上的E233P/L234V/L235A/G236del/S267K消融变体。主链4基于人IgG1(356E/358M同种异型)，并且包含D401K:K360E/Q362E/T411E偏斜变体、具有K360E/Q362E/T411E偏斜变体的链上的N208D/Q295E/N384D/Q418E/N421D pI变体、以及两条链上的E233P/L234V/L235A/G236del/S267K消融变体。主链5基于人IgG1(356D/358L同种异型)，并且包含S364K/E357Q:L368D/K370S偏斜变体、在具有L368D/K370S偏斜变体的链上的N208D/Q295E/N384D/Q418E/N421D pI变体，以及两条链上的E233P/L234V/L235A/G236del/S267K消融变体。主链6基于人IgG1(356E/358M同种异型)，并且包含S364K/E357Q:L368D/K370S偏斜变体、具有L368D/K370S偏斜变体的链上的N208D/Q295E/N384D/Q418E/N421DpI变体、和两条链上的E233P/L234V/L235A/G236del/S267K消融变体，以及两条链上的N297A变体。除了突变是N297S之外，主链7与主链6相同。除了主链8包含M428L/N434S Xtend突变之外，主链8与主链1相同。主链9基于人IgG1(356E/358M同种异型)，并且包含S364K/E357Q:L368D/K370S偏斜变体、具有S364K/E357Q偏斜变体的链上的P217R/P229R/N276K pI变体、以及两条链上的E233P/L234V/L235A/G236del/S267K消融变体。在这些主链的每一条主链内包括与所列举的序列90％、95％、98％和99％相同(如本文所定义)和/或含有1个、2个、3个、4个、5个、6个、7个、8个、9个或10个另外的氨基酸取代的序列(与附图的“亲本”相比，如本领域技术人员将理解，与亲本人IgG1(或IgG2或IgG4，这取决于主链)相比，已经含有多个氨基酸修饰)。即，除了此图的主链中所含的偏斜变体、pI变体和消融变体之外，所列举主链可以含有另外的氨基酸修饰(通常是氨基酸取代)。
图9描绘了基于人IgG1的几个有用的恒定轻链结构域主链的序列，没有Fv序列(例如scFv或Fab)。本文包含的恒定轻主链序列与所列举的序列是90％、95％、98％和99％同一的(如本文所定义)，和/或含有1个、2个、3个、4个、5个、6个、7个、8个、9个或10个另外的氨基酸修饰。
图10A至图10F描绘了适合用于本发明的双特异性抗体中的示例性抗CD3 scFv的序列。CDR加下划线，scFv接头加双下划线(在序列中，scFv接头是带正电荷的scFv(GKPGS)4接头(SEQ ID NO:15)，但是如本领域的技术人员将理解的，这个接头可以被其他接头替换，包含不带电荷的接头或带负电荷的接头，其中一些描绘在图5中)，并且斜线指示可变结构域的边界。另外，命名约定展示了scFv从N末端到C末端的取向。如本文中所指出并且对本文中含有CDR的每一序列而言确实如此，如表2中所示，取决于所使用的编号，CDR位置的精确标识可能略微不同，并且因此本文中不仅包括带下划线的CDR并且还包括使用其他编号系统的VH和VL结构域内所包括的CDR。此外，如对于附图中的所有序列，这些VH和VL序列可以scFv形式或Fab形式使用。
图11A至图11B描绘了本发明中使用的多种抗原的抗原序列(包括人和食蟹猴(cyno)两者)，以促进开发易于临床开发的结合到两者的抗原结合结构域。
图12描绘了人源化GPC3-A变体的可变重链序列和可变轻链序列。CDR加有下划线，并且斜线指示可变区与恒定结构域之间的边界。如本文中所指出并且对本文中含有CDR的每一序列而言确实如此，如表2中所示，取决于所使用的编号，CDR位置的精确标识可能略微不同，并且因此本文中不仅包括带下划线的CDR并且还包括使用其他编号系统的VH和VL结构域内所包括的CDR。进一步，如对于附图中的所有序列，这些VH和VL序列可以scFv形式或Fab形式使用。此外，本文描绘的可变重链结构域中的每个可变重链结构域可以与任何其他αGPC3-A可变轻链结构域配对；并且本文描绘的可变轻链结构域中的每个可变轻链结构域可以与任何其他αGPC3-A可变重链结构域配对。
图13A至图13G描绘了GPC3-A变体的可变重链序列和可变轻链序列，该变体被工程化以减少降解(例如天冬氨酸异构化和脱酰胺)倾向、调节GPC3结合亲和力和/或对高GPC3表达细胞系的选择性。CDR加有下划线，并且斜线指示可变区与恒定结构域之间的边界。如本文中所指出并且对本文中含有CDR的每一序列而言确实如此，如表2中所示，取决于所使用的编号，CDR位置的精确标识可能略微不同，并且因此本文中不仅包括带下划线的CDR并且还包括使用其他编号系统的VH和VL结构域内所包括的CDR。进一步，如对于附图中的所有序列，这些VH和VL序列可以scFv形式或Fab形式使用。此外，本文描绘的可变重链结构域中的每个可变重链结构域可以与任何其他αGPC3可变轻链结构域配对；并且本文描绘的可变轻链结构域中的每个可变轻链结构域可以与任何其他αGPC3可变重链结构域配对。
图14A至图14E描绘了被格式化为具有E233P/L234V/L235A/G236del/S267K消融变体的二价抗GPC3 mAb和IgG1主链的说明性GPC3-A变体。CDR加有下划线，并且斜线指示可变区与恒定结构域之间的边界。如本文中所指出并且对本文中含有CDR的每一序列而言确实如此，如表2中所示，取决于所使用的编号，CDR位置的精确标识可能略微不同，并且因此本文中不仅包括带下划线的CDR并且还包括使用其他编号系统的VH和VL结构域内所包括的CDR。此外，如对于附图中的所有序列，这些VH和VL序列可以scFv形式或Fab形式使用。
图15A至图15B描绘了本发明的几种形式。图15A描绘了具有结合GPC3的第一Fab臂和结合CD3的第二scFv臂的“1+1 Fab-scFv-Fc”形式。图15B描绘了具有结合GPC3的第一Fab臂和第二Fab-scFv臂的“2+1 Fab2-scFv-Fc”形式，其中Fab结合GPC3并且scFv结合CD3。
图16A至图16C描绘了呈1+1 Fab-scFv-Fc形式并包含CD3高scFv(VHVL取向或VLVH取向的H1.30_L1.47)的说明性αGPC3×αCD3 bsAb的序列。CDR加有下划线，并且斜线指示可变区与其他链组分(例如恒定区和结构域接头)之间的边界。应注意，αGPC3×αCD3 bsAb可以利用90％、95％、98％和99％相同(如本文所定义)和/或含有1个、2个、3个、4个、5个、6个、7个、8个、9个或10个氨基酸取代的可变区、Fc区和恒定结构域序列。另外，本文概述的每个序列均可以包含或不包含一个或优选地两个Fc结构域中的M428L/N434S变体，这产生了较长的血清半衰期。
图17A至图17G描绘了呈1+1 Fab-scFv-Fc形式并包含CD3高-Int编号1scFv(VHVL取向或VLVH取向的H1.32_L1.47)的说明性αGPC3×αCD3 bsAb的序列。CDR加有下划线，并且斜线指示可变区与其他链组分(例如恒定区和结构域接头)之间的边界。应注意，αGPC3×αCD3 bsAb可以利用90％、95％、98％和99％相同(如本文所定义)和/或含有1个、2个、3个、4个、5个、6个、7个、8个、9个或10个氨基酸取代的可变区、Fc区和恒定结构域序列。另外，本文概述的每个序列均可以包含或不包含一个或优选地两个Fc结构域中的M428L/N434S变体，这产生了较长的血清半衰期。
图18A至图18B描绘了呈2+1 Fab2-scFv-Fc形式并包含CD3高scFv(VHVL取向或VLVH取向的H1.30_L1.47)的说明性αGPC3×αCD3 bsAb的序列。CDR加有下划线，并且斜线指示可变区与其他链组分(例如恒定区和结构域接头)之间的边界。应注意，αGPC3×αCD3bsAb可以利用90％、95％、98％和99％相同(如本文所定义)和/或含有1个、2个、3个、4个、5个、6个、7个、8个、9个或10个氨基酸取代的可变区、Fc区和恒定结构域序列。另外，本文概述的每个序列均可以包含或不包含一个或优选地两个Fc结构域中的M428L/N434S变体，这产生了较长的血清半衰期。
图19A至图19H描绘了呈2+1 Fab2-scFv-Fc形式并包含CD3高-Int编号1scFv(VHVL取向或VLVH取向的H1.32_L1.47)的说明性αGPC3×αCD3 bsAb的序列。CDR加有下划线，并且斜线指示可变区与其他链组分(例如恒定区和结构域接头)之间的边界。应注意，αGPC3×αCD3 bsAb可以利用90％、95％、98％和99％相同(如本文所定义)和/或含有1个、2个、3个、4个、5个、6个、7个、8个、9个或10个氨基酸取代的可变区、Fc区和恒定结构域序列。另外，本文概述的每个序列均可以包含或不包含一个或优选地两个Fc结构域中的M428L/N434S变体，这产生了较长的血清半衰期。
图20A至图20E描绘了呈2+1 Fab2-scFv-Fc形式并包含CD3高-Int编号2scFv(VHVL取向或VLVH取向的H1.89_L1.47)的说明性αGPC3×αCD3 bsAb的序列。CDR加有下划线，并且斜线指示可变区与其他链组分(例如恒定区和结构域接头)之间的边界。应注意，αGPC3×αCD3 bsAb可以利用90％、95％、98％和99％相同(如本文所定义)和/或含有1个、2个、3个、4个、5个、6个、7个、8个、9个或10个氨基酸取代的可变区、Fc区和恒定结构域序列。另外，本文概述的每个序列均可以包含或不包含一个或优选地两个Fc结构域中的M428L/N434S变体，这产生了较长的血清半衰期。
图21描绘了呈2+1 Fab2-scFv-Fc形式并包含CD3中间体scFv(VHVL取向或VLVH取向的H1.33_L1.47)的说明性αGPC3-A×αCD3 bsAb的序列。CDR加有下划线，并且斜线指示可变区与其他链组分(例如恒定区和结构域接头)之间的边界。应注意，αGPC3-A×αCD3 bsAb可以利用90％、95％、98％和99％相同(如本文所定义)和/或含有1个、2个、3个、4个、5个、6个、7个、8个、9个或10个氨基酸取代的可变区、Fc区和恒定结构域序列。另外，本文概述的每个序列均可以包含或不包含一个或优选地两个Fc结构域中的M428L/N434S变体，这产生了较长的血清半衰期。
图22描绘了基于WO 2016/047722中公开的比较物αGPC3×αCD3双特异性抗体的序列。
图23描绘了5种GPC-A亲和力变体H1.1_L1.6、H1.1_L1.29、H1.1_L1.16、H1.1_L1.23和H1.1_L1.31(格式化为具有CD3高-Int编号1scFv的1+1 Fab-scFv-Fc)对人和食蟹猴GPC3抗原的结合亲和力。亲和力变体显示出宽范围的结合(4nM-400nM KD)并且对食蟹猴(cynomolgus)GPC3具有交叉反应性。
图24描绘了3种GPC-A亲和力变体H1.1_L1.29、H1.1_L1.16和H1.1_L1.31(格式化为具有CD3高-Int编号1scFv的1+1 Fab-scFv-Fc)与HepG2(GPC3高)细胞的结合。
图25描绘了被工程化以消除降解倾向的GPC3-A变体与人GPC3-A的结合。几种变体显示出对GPC3的结合亲和力降低。
图26描绘被工程化以消除降解倾向的GPC3-A变体与人和食蟹猴GPC3-A的结合。几种变体显示出与GPC3的结合降低、双相性或消除。
图27描绘了通过αGPC3×αCD3 bsAb比较物XENP31308对A)RTCC的诱导以及对B)T细胞的活化(如IFNγ分泌所指示)。XENP31308在GPC3高HepG2细胞、GPC3中等Huh7细胞和GPC3低HEK293细胞中的每一者存在的情况下诱导有效的RTCC和T细胞的活化(10:1的效应物:靶标比率)。
图28描绘了以1:1效应物:靶标比率通过αGPC3×αCD3 bsAb比较物XENP31308对A)RTCC的诱导以及对B)T细胞的活化(如IFNγ分泌所指示)。
图29描绘了在HepG2(GPC3高)细胞存在的情况下，通过结合格式化为具有CD3高-Int编号1的2+1 Fab2-scFv-Fc bsAb的不同GPC3表位的GPC3结合结构域对T细胞的活化(如IFNγ释放所指示)。具有除GPC3-A以外的GPC3结合结构域的每个bsAb活化T细胞的效力低于具有GPC3-A结合结构域的bsAb。
图30描绘了在1+1 Fab-scFv-Fc bsAb、2+1 Fab2-scFv-Fc bsAb和二价单特异性mAb的情形中A)GPC3-A H1.1_L1.16(100nM)变体和B)GPC3-A H1.1_L1.31(400nM)变体与HepG2(GPC3高)的结合。与1+1形式的bsAb相比，2+1形式的BsAb显示出更有效的结合(并与二价单特异性mAb的结合相当)。对于较低结合亲和力的GPC3-A_H1.1_L1.31(400nM)变体，从1+1形式到2+1形式的效力转变更为明显。
图31描绘了A)RTCC的诱导和B)在HepG2(GPC3高)细胞与T细胞(10:1效应物:靶标比率)和具有不同CD3结合亲和力的1+1 Fab-scFv-Fc形式的αGPC3×αCD3 bsAb一起孵育后T细胞的细胞因子释放。将CD3结合亲和力从CD3高失调到CD3高-Int编号1提供了RTCC效力的显著降低，并且更重要的是，IFNγ释放潜在地减轻细胞因子释放综合征。
图32描绘了A)RTCC的诱导和B)在HepG2(GPC3高)细胞与T细胞(10:1效应物:靶标比率)和具有不同CD3结合亲和力的2+1 Fab2-scFv-Fc形式的αGPC3×αCD3 bsAb一起孵育后T细胞的细胞因子释放。将CD3结合亲和力从CD3高失调到CD3高Int编号1不提供效力的显著降低，但进一步降低到CD3高-Int编号2的确提供效力的显著降低。
图33描绘了A)RTCC的诱导和B)在HepG2(GPC3高)细胞存在的情况下，通过格式化为具有CD3高-Int编号2[VLVH]scFv的2+1 Fab2-scFv-Fc的3个GPC3-A亲和力变体的细胞因子分泌。bsAb以与其亲和力降低相关的方式诱导RTCC，其中具有70nm GPC3亲和力变体的XENP37625显示出最强的效力，并且具有400nM GPC3亲和力变体的XENP37626显示出最弱的效力。令人惊讶的是，H1.1_L1.23 200nM亲和力变体似乎与400nM亲和力变体没有显著区别。
图34描绘了通过本发明的另外的αGPC3×αCD3 bsAb(XENP36935、XENP37430、XENP34364、XENP34920、XENP35843、XENP36939和XENP37433)以1:1效应物:靶标比率在A)HepG2细胞和B)HEK293细胞上RTCC的诱导。
图35描绘了以1:1效应物:靶标比率在A)HepG2细胞和B)HEK293细胞以及本发明的另外的αGPC3×αCD3 bsAb(XENP36935、XENP37430、XENP34364、XENP34920、XENP35843、XENP36939和XENP37433)存在的情况下T细胞对IFNγ释放的诱导。XENP37430和XENP34920显示出对HepG2的最高效力，而XENP36939具有最低效力。每种bsAb诱导IFNγ释放的效力与其在RTCC诱导中的效力成比例。与HEK293(GPC低)相比，大多数bsAb选择性在HepG2(GPC高)存在的情况下诱导杀伤(和细胞因子释放)。
图36描绘了通过本发明的αGPC3×αCD3 bsAb(XENP36935、XENP37430、XENP37625、XENP35843、XENP34920、XENP37624、XENP36939、XENP37433和XENP37626)和比较物bsAbXENP31308以10:1效应物:靶标比在HepG2上RTCC的诱导。BsAb XENP34920、XENP37430、XENP37625和XENP37624显示出与比较物XENP31308类似的效力(EC50小于100ng/ml)。其他bsAb XENP35843、XENP36935、XENP37433和XENP37626的效力低得多，但能够在更高浓度下实现有效杀伤。XENP36939没有显示任何杀伤。
图37描绘了通过本发明的αGPC3×αCD3 bsAb(XENP36935、XENP37430、XENP37625、XENP35843、XENP34920、XENP37624、XENP36939、XENP37433和XENP37626)和比较物bsAbXENP31308以1:1效应物:靶标比在HepG2上RTCC的诱导。
图38描绘了通过本发明的αGPC3×αCD3 bsAb(XENP36935、XENP37430、XENP37625、XENP35843、XENP34920、XENP37624、XENP36939、XENP37433和XENP37626)和比较物bsAbXENP31308以10:1效应物:靶标比在Huh7上RTCC的诱导。
图39描绘了在2D Incucyte模型中GPC3高HepG2肿瘤随时间推移的生长。使用每个测试品的10ug/ml处理浓度和10:1的E:T比率。如在其他Incucyte研究中所见，XENP36939没有显示任何显著的活性，其功效类似于PBS对照。然而，包括XENP34920、XENP37430、XENP36935、XENP37624和XENP37625的大多数其他测试显示出与比较物XENP31308类似的功效。
图40描绘了在2D Incucyte模型中GPC3中等Huh7肿瘤细胞随时间推移的生长。使用每个测试品的10ug/ml处理浓度。具有400nM GPC3结合物的bsAb(XENP36939、XENP37433或XENP37626)都不能显著抑制细胞生长。然而，具有70nM或100nM GPC3结合物的2+1bsAb都能够以与比较物类似的功效阻止生长。
图41描绘了使用Incucyte的3D球体RTCC模型的结果。将1,000个HepG2细胞(倍增时间为24小时)接种在孔中并给予72小时-96小时生长，然后添加40,000个PBMC(导致E:T比率为约3:1)以及浓度为10ug/ml的指示bsAb。每个信号(肿瘤细胞或免疫细胞)的强度在每个孔上进行积分。考虑到与XENP36935(高-In编号1)相比，XENP37625具有较低的亲和力CD3臂(高-Int编号2)，XENP34920和XENP37624的曲线比预期更相似。144小时后，除XENP36939外的所有bsAb显示100％功效。
图42描绘了使用Incucyte的3D球体RTCC模型的结果。将1,000个HepG2细胞(倍增时间为24小时)接种在孔中并给予72小时-96小时生长，然后添加40,000个PBMC(导致E:T比率为约3:1)以及浓度为10ug/ml的指示bsAb。每个信号(肿瘤细胞或免疫细胞)的强度在每个孔上进行积分。有趣的是，一种较弱亲和力的400nM GPC3结合物显示最高水平的增殖。除了1+1构建体XENP35843和XENP36939外，其余的bsAb显示与比较物XENP31308相似或更高水平的免疫细胞增殖。
图43描绘了拍摄使用Incucyte的3D球体RTCC模型的结果的照片。将1,000个HepG2细胞(倍增时间为24小时)接种在孔中并给予72小时-96小时生长，然后添加40,000个PBMC(导致E:T比率为约3:1)以及浓度为10ug/ml的指示bsAb。在PBS对照柱中可以最清楚地看到靶肿瘤细胞球体，其中PBMC聚集在球体周围并随时间推移保持不变。在将PBS对照柱与由XENP31308、XENP37625、XENP34920和XENP36935处理的柱进行比较时，可以观察到当免疫细胞杀死肿瘤细胞时PBMC的扩增。
图44A至图44J描绘了本发明的几种形式。第一个是1+1 Fab-scFv-Fc形式，具有第一抗抗原结合结构域和第二抗抗原结合结构域。另外，mAb-Fv、mAb-scFv、中心-scFv、中心-Fv、单臂中心-scFv、单scFv-mAb、scFv-mAb和双scFv形式均已展示。对于所描绘的所有scFv结构域，其可以是由N末端到C末端，可变重链-(任选的接头)-可变轻链，或相反。另外，对于单臂scFv-mAb，scFv可以附接至重链单体的N末端或附接至轻链的N末端。
具体实施方式
本发明提供了结合到人CD3ε和人GPC3的异二聚双特异性抗体。
A.概述
共同结合CD3和肿瘤抗原靶标的抗双特异性抗体用于重定向T细胞以攻击和裂解靶向的肿瘤细胞。示例包括和DART形式，它们单价结合CD3和肿瘤抗原。虽然靶向CD3的方法已显示出相当大的前景，但此类疗法的常见副作用是相关的细胞因子产生，往往会导致毒性细胞因子释放综合征。由于双特异性抗体的抗CD3结合结构域与所有T细胞结合，因此募集了高产生细胞因子的CD4 T细胞亚群。此外，CD4 T细胞亚群包括调节性T细胞，所述调节性T细胞的募集和扩增可能会导致免疫抑制并对长期肿瘤抑制具有负面影响。此外，这些形式不包含Fc结构域并且在患者中显示出非常短的血清半衰期。
本文提供了新型的抗CD3×抗GPC3(也称为抗GPC3×抗CD3、αCD3×αGPC3、αGPC3×αCD3或有时仅为GPC3 X CD3)异二聚双特异性抗体和使用此类抗体用于治疗癌症的方法。具体地，本文提供了多种形式的抗CD3、抗GPC3双特异性抗体。这些双特异性抗体可用于治疗癌症，尤其是那些GPC3表达增加的癌症，诸如肾细胞癌。此类抗体用于将CD3+效应T细胞引导到GPC3+肿瘤，从而允许CD3+效应T细胞攻击并裂解GPC3+肿瘤。
此外，在一些实施方案中，本公开提供了对人CD3具有不同结合亲和力的双特异性抗体，该双特异性抗体可以改变或减少抗CD3疗法的潜在副作用。也就是说，在一些实施方案中，本文所述的抗体提供了抗体构建体，抗体构建体包含抗CD3抗原结合结构域，抗CD3抗原结合结构域是与CD3的“强”或“高亲和力”结合物(例如，一个示例是描述为H1.30_L1.47的重链可变结构域和轻链可变结构域(任选地包括适当的带电荷接头))并且还与GPC3结合。在其它实施方案中，本文所述的抗体提供了抗体构建体，抗体构建体包含抗CD3抗原结合结构域，抗CD3抗原结合结构域是与CD3的“轻度”或“低亲和力”结合物。另外的实施方案提供了抗体构建体，抗体构建体包含抗CD3抗原结合结构域，抗CD3抗原结合结构域对也结合GPC3的CD3具有中度或“中等”亲和力。虽然可以使用非常大量的抗CD3抗原结合结构域(ABD)，但特别有用的实施方案使用6种不同的抗CD3 ABD，尽管它们可以如本文所讨论的以两种scFv取向使用。通常使用Biacore测定测量亲和力。
应当理解的是，本文提供的“高、中、低”抗CD3序列可以如本文所讨论的多种异二聚化形式使用。通常，由于T细胞募集的潜在副作用，例示性的施方式利用仅单价结合CD3的形式，例如图15A和图15B中描绘的，并且在本文描绘的形式中，CD3 ABD是如本文更充分描述的scFv。相比之下，本发明双特异性抗体可以单价(例如图15A)或二价(例如图15B)地结合GPC3。
本文提供了包含GPC3结合结构域的组合物，组合物包含具有此类GPC3结合结构域的抗体(例如，GPC3×CD3双特异性抗体)。包含此类GPC3结合结构域的本发明抗体有利地引发一系列不同的免疫应答，这取决于所使用的特定GPC3结合结构域。例如，本发明抗体在对具有不同GPC3表达的细胞的选择性、对于GPC3表达性细胞的效力、引发细胞因子释放的能力以及对可溶性GPC3的敏感性方面表现出差异。此类GPC3结合结构域和相关的抗体可用于例如治疗GPC3相关癌症。
因此，在一个方面中，本文提供了与两种不同抗原结合的异二聚抗体，例如抗体是“双特异性的”，因为抗体与两种不同的靶抗原结合，通常是如本文所述的GPC3和CD3。这些异二聚抗体可以与这些靶抗原(例如，存在单个抗原结合结构域，如可变重链和可变轻链结构域对)或二价地(存在各自独立地与抗原结合的两个抗原结合结构域)单价地结合。在一些实施方案中，本文提供的异二聚抗体包含一个CD3结合结构域和一个GPC3结合结构域(例如，本文描述的“1+1 Fab-scFv-Fc”形式的异二聚抗体)。在其他实施方案中，本文提供的异二聚抗体包括一个CD3结合结构域和两个GPC3结合结构域(例如，本文描述的“2+1 Fab2-scFv-Fc”形式的异二聚抗体)。本文提供的异二聚抗体基于使用不同的单体，不同的单体含有使异二聚体相比于同源二聚体“偏斜”形成的氨基酸取代，如以下更完整地概述的，不同的单体与允许异二聚体远离同源二聚体的简单纯化的“pI变体”结合，如以下类似地概述的。所提供的异二聚体双特异性抗体通常依赖于使用可以在生产细胞中自组装以产生异二聚体蛋白的工程化或变体Fc结构域，以及产生和纯化此类异二聚体蛋白的方法。
B.命名法
本文提供的抗体以若干种不同的形式列出。在一些实例中，特定抗体中的每个单体被给予唯一的“XENP”编号，但是如本领域中将理解的，较长的序列可能含有较短的XENP编号。例如，1+1 Fab-scFv-Fc形式抗体的“scFv-Fc”单体可以具有第一XENP编号，而scFv结构域本身将具有不同的XENP编号。一些分子具有三个多肽，因此在具有组分的情况下，XENP编号用作名称。因此，呈2+1 Fab2-scFv-Fc形式的分子XENP33744包含三个序列(参见图18)：“Fab-Fc重链”单体；2)“Fab-scFv-Fc重链”单体；和3)“轻链”单体或等同物，尽管本领域技术人员能够通过序列比对容易地鉴定这些。这些XENP编号在序列表以及标识符中，并且在附图中使用。另外，一个包含三种组分的分子产生多个序列标识符。例如，Fab的列表包括全重链序列、可变重链结构域序列和可变重链结构域序列的三个CDR、全轻链序列、可变轻链结构域序列和可变轻链结构域序列的三个CDR。Fab-scFv-Fc单体包括全长序列、可变重链结构域序列、3个重链CDR序列和一个scFv序列(包括scFv可变重链结构域序列、scFv可变轻链结构域序列和scFv接头)。应注意，本文中具有scFv结构域的一些分子使用单个带电荷的scFv接头(+H)，但也可以使用其它的。另外，特定抗原结合结构域(例如，GPC3和CD3结合结构域)的术语命名法使用“Hx.xx_Ly.yy”类形式，其中编号作为特定可变链序列的唯一标识符。因此，抗原结合结构域的Fv结构域是“H1 L1”，其指示可变重链结构域H1与轻链结构域L1组合。在这些序列用作scFv的情况下，名称“H1 L1”指示可变重链结构域，H1与轻结构域L1组合并且从N末端到C末端处于VH-接头-VL取向。具有重链可变结构域和轻链可变结构域的相同序列但是所述序列处于倒序(从N末端到C末端是VL-接头-VH取向)的这种分子将被命名为“L1_H1.1”。类似地，不同构建体可能“混合和匹配”重链和轻链，如从序列表和附图中将显而易见的。
另外，本发明的双特异性抗体在本文中称为“抗CD3×抗GPC3”、“αCD3×αGPC3”、“αGPC3×αCD3”或有时仅称为“GPC3 X CD3”。如将在下文中所讨论，抗原的顺序不是决定性的，尽管大多数用作scFv的形式具有作为scFv的抗CD3 ABD。
C.定义
为了可以更全面地理解本申请，下面阐述几个定义。此类定义意在涵盖语法等同物。
本文中的“GPC3”意指属于密封蛋白家族的蛋白质。GPC3序列描绘在例如图11中。本发明的ABD与人GPC3结合。
本文中的“消融”意指活性的降低或去除。因此例如，“消融FcγR结合”意指Fc区氨基酸变体与不含特异性变体的Fc区相比具有少于50％的起始结合，优选大于70％-80％-90％-95％-98％的活性损失，并且通常，活性低于Biacore、SPR或BLI测定中的可检测结合的水平。特别用于FcγR结合的消融的是图3所示的那些变体，所述变体通常添加到两个单体中。
如本文所用，“ADCC”或“抗体依赖性细胞介导的细胞毒性”意指其中表达FcγR的非特异性细胞毒性细胞识别靶细胞上的结合抗体并且随后引起靶细胞裂解的细胞介导反应。ADCC与结合FcγRIIIa相关；与FcγRIIIa结合的增加引起ADCC活性的增加。
如本文所用，“ADCP”或抗体依赖性细胞介导的吞噬意指其中表达FcγR的非特异性吞噬细胞识别靶细胞上的结合抗体并且随后引起靶细胞吞噬的细胞介导反应。
如本文所用，通常使用术语“抗体”。本文所述的抗体可以采取如本文所述的多种形式，包括传统抗体以及抗体衍生物、片段和模拟物，包括本文所述的多种双特异性形式。
传统的免疫球蛋白(Ig)抗体是“Y”形四聚体。每个四聚体通常由两对相同的多肽链构成，每对具有一个“轻链”单体(通常分子量为约25kDa)和一个“重链”单体(通常分子量为约50kDa-70kDa)。
其他有用的抗体形式包括但不限于本文所述和图15中所描绘的1+1Fab-scFv-Fc形式和2+1 Fab-scFv-Fc抗体形式，以及如下文所讨论和图44中示出的“mAb-Fv”、“mAb-scFv”、“中心-Fv”、“单臂scFv-mAb”、“scFv-mAb”、“双scFv”和“三叉”形式抗体。
抗体重链通常包含可变重链(VH)结构域，该可变重链结构域包含vhCDR1-3和Fc结构域，该Fc结构域包含CH2-CH3单体。在一些实施方案中，抗体重链包含铰链和CH1结构域。传统的抗体重链是从N末端到C末端如下组织的单体：VH-CH1-铰链-CH2-CH3。CH1-铰链-CH2-CH3统称为抗体的重链“恒定结构域”或“恒定区”，其中有五种不同的类别或“同种型”：IgA、IgD、IgG、IgE和IgM。因此，如本文所用的“同种型”意指通过其恒定区的化学和抗原特征界定的免疫球蛋白的任一亚类。应当理解，治疗性抗体还可以包含同种型和/或亚类的杂交体。例如，如在以引用方式并入的美国公开2009/0163699中所示，本文所述的抗体包含使用人IgG1/G2杂交体。
在一些实施方案中，本文提供的抗体包括IgG同种型恒定结构域，该IgG同种型恒定结构域具有若干亚类，包括但不限于IgG1、IgG2、IgG3和IgG4。在免疫球蛋白的IgG亚类中，重链中存在几种免疫球蛋白结构域。“免疫球蛋白(Ig)结构域”在本文中意指具有不同三级结构的免疫球蛋白区域。本文所述的抗体中感兴趣的是重链结构域，包括恒定重链(CH)结构域和铰链结构域。在IgG抗体的上下文中，IgG同种型各自具有三个CH区。因此，在IgG的上下文中，“CH”结构域如下：“CH1”是指根据如Kabat中的EU索引的位置118-220。“CH2”是指根据如Kabat中的EU索引的位置237-340，并且“CH3”是指根据如Kabat中的EU索引的位置341-447。如本文所示和下文所描述，pI变体可以处于CH区的一个或多个CH区以及铰链区中，如下文所讨论。
应注意，IgG1具有在356(D或E)和358(L或M)处具有多型性的不同同种异型。本文描绘的序列使用356D/358M同种异型，然而本文包括其他同种异型。也就是说，本文包括的包含IgG1 Fc结构域的任何序列可以具有替代356D/358M同种异型的356E/358L。应当理解，治疗性抗体还可以包含同种型和/或亚类的杂交体。例如，如以引用方式并入的美国公开2009/0163699中所示，本发明的抗体在一些实施方案中包含IgG1/IgG2杂交体。
如本文所用，“Fc”或“Fc区”或“Fc结构域”指多肽，该多肽包含抗体的恒定区，在一些情况下不包含所有第一恒定区免疫球蛋白结构域(例如，CH1)或其一部分，并且在一些情况下，任选地包括铰链的全部或一部分。对于IgG，Fc结构域包括免疫球蛋白结构域CH2和CH3(Cγ2和Cγ3)，以及任选地CH1(Cγ1)与CH2(Cγ2)之间的铰链区的全部或一部分。因此，在一些情况下，Fc结构域从N末端到C末端包括CH2-CH3和铰链-CH2-CH3。在一些实施方案中，Fc结构域是来自人IgG1、IgG2、IgG3或IgG4的Fc结构域，其中人IgG1铰链-CH2-CH3和IgG4铰链-CH2-CH3特别用于许多实施方案中。另外，在人IgG1 Fc结构域的情况下，铰链时常包括C220S氨基酸取代。另外，在人IgG4 Fc结构域的情况下，铰链时常包括S228P氨基酸取代。尽管Fc区的边界可以变化，但人IgG重链Fc区通常被定义成在其羧基末端包含残基E216、C226或A231，其中编号是根据如Kabat中的EU索引进行的。在一些实施方案中，如下文更全面地描述，对Fc区进行氨基酸修饰，例如以改变与一种或多种FcγR或FcRn的结合。
本文中的“重链恒定区”意指抗体(或其片段)的CH1-铰链-CH2-CH3部分，不包括可变重链结构域；在人IgG1的EU编号中，这是氨基酸118-447。本文中的“重链恒定区片段”意指从N末端和C末端中的任一者或两者含有较少氨基酸但仍保持能够与另一个重链恒定区形成二聚体的重链恒定区。
重链的另一种类型的Ig结构域是铰链区。本文的“铰链”或“铰链区”或“抗体铰链区”或“铰链结构域”意指包括抗体的第一恒定结构域与第二恒定结构域之间的氨基酸的柔性多肽。在结构上，IgG CH1结构域在EU位置215处终止，并且IgG CH2结构域在残基EU位置231处开始。因此本文中对于IgG而言定义抗体铰链包含位置216(在IgG1中为E216)至230(在IgG1中为p230)，其中编号是根据如Kabat中的EU索引进行的。在一些情况下，使用“铰链片段”，其在铰链结构域的N末端和C末端中任一个或两个处含有较少氨基酸。如本文所指出，pI变体还可以在铰链区中制成。在本文中许多抗体具有被被丝氨酸代替的在根据EU编码(铰链区)的位置220处的至少一个半胱氨酸。通常，这种修饰在本文所描绘的大多数序列的“scFv单体”侧上，但是其也可以是在“Fab单体”侧上或在两者上以减少二硫化物形成。本文序列中特别包括这些半胱氨酸中的一个或两个被替代(C220S)。
如本领域技术人员将理解的，重链恒定区结构域的确切编号和放置在不同编号系统之间可以是不同的。根据EU和Kabat的重链恒定区编号的有用比较如下，参见Edelman等人，1969，美国国家科学院院刊(Proc Natl Acad Sci USA)63:78-85和Kabat等人，1991，免疫学相关蛋白质的序列(Sequences of Proteins of Immunological Interest)，第5版，贝塞斯达美国国家卫生研究院公共卫生服务部(United States Public Health Service,National Institutes of Health,Bethesda)，这些文献以引用方式整体并入本文中。
表1
抗体轻链通常包含两个结构域：可变轻链结构域(VL)，该可变轻链结构域包含轻链CDR vlCDR1-3，以及恒定轻链区(往往称为CL或Cκ)。抗体轻链通常从N末端到C末端如下组织：VL-CL。
本文中的“抗原结合结构域”或“ABD”意指一组六个互补决定区(CDR)在作为多肽序列的一部分存在时与如本文所讨论的靶抗原(例如，GPC3或CD3)特异性地结合。如本领域中已知，这些CDR通常作为第一组可变重链CDR(vhCDR或VHCDR)和第二组可变轻链CDR(vlCDR或VLCDR)存在，其各自包含三个CDR：vhCDR1可变重链CDR、vhCDR2可变重链CDR、vhCDR3可变重链CDR和vlCDR1可变轻链CDR、vlCDR2可变轻链CDR和vlCDR3 vhCDR3可变轻链CDR。CDR存在于可变重链结构域(vhCDR1-3)和可变轻链结构域(vlCDR1-3)中。可变重链结构域和可变轻链结构域形成Fv区。
本文所述的抗体提供大量不同的CDR组。在这种情况下，“完整CDR组”包含三个可变轻链和三个可变重链CDR，例如vlCDR1、vlCDR2、vlCDR3、vhCDR1、vhCDR2和vhCDR3。这些可以分别是较大可变轻链结构域或可变重链结构域的一部分。另外，如本文中更全面地概述的，当使用重链和轻链时(例如当使用Fab时)，可变重链结构域和可变轻链结构域可以在单独的多肽链上，或在scFv序列的情况下在单个多肽链上。
如本领域技术人员将理解的，CDR的确切编号和放置在不同编号系统之间可以是不同的。然而，应理解，可变重链序列和/或可变轻链序列的公开内容包括相关(固有)CDR的公开内容。因此，每个可变重区的公开内容是vhCDR的公开内容(例如，vhCDR1、vhCDR2和vhCDR3)，并且每个可变轻区的公开内容是vlCDR的公开内容(例如，vlCDR1、vlCDR2和vlCDR3)。CDR编号的有用比较如下，参见Lafranc等人，《发展与比较免疫学(Dev.Comp.Immunol.)》27(1):55-77(2003)：
表2
在整个本说明书中，当提及可变结构域(大致是轻链可变区的残基1-107和重链可变区的残基1-113)中的残基以及用于Fc区的EU编号系统时，通常使用Kabat编号系统(例如Kabat等人，见上文(1991))。
CDR有助于形成抗原结合结构域和抗体的抗原结合位点，或更具体来说，表位结合位点。“表位”是指与称为互补位的抗体分子可变区中的特定抗原结合位点相互作用的决定簇。表位是诸如氨基酸或糖侧链的分子的分组，并且通常具有特定的结构特征以及特定的电荷特征。单个抗原可具有多于一个表位。
表位可以包含直接参与结合的氨基酸残基(也称为表位的免疫显性组分)和不直接参与结合的其他氨基酸残基，诸如被特异性抗原结合肽有效阻断的氨基酸残基；换句话说，氨基酸残基在特异性抗原结合肽的覆盖面积内。
表位可以是构象的或线性的。通过来自线性多肽链的不同区段的空间并置的氨基酸产生构象表位。线性表位是由多肽链中的相邻氨基酸残基产生的表位。构象表位和非构象表位的区别可以在于在变性溶剂存在下，与前者而非后者的结合丧失。
表位通常包括独特空间构象中的至少3个，并且更通常至少5个或8个-10个氨基酸。识别相同表位的抗体可以在简单的免疫分析中验证，所述免疫分析显示一种抗体阻断另一种抗体与靶抗原结合的能力，例如“分箱”。如下所述，本公开不仅包括本文列举的抗原结合结构域和抗体，还包括竞争与所列举的抗原结合结构域结合的表位结合的抗原结合结构域和抗体。
在一些实施方案中，抗原结合结构域的六个CDR源自可变重链结构域和可变轻链结构域。在“Fab”形式中，该组6个CDR源自两个不同的多肽序列、可变重链结构域(vh或VH；含有vhCDR1、vhCDR2和vhCDR3)和可变轻链结构域(vl或VL；含有vlCDR1、vlCDR2和vlCDR3)，其中vh结构域的C末端附接至重链的CH1结构域的N末端，并且vl结构域的C末端附接至恒定轻链结构域的N末端(从而形成轻链)。在scFv形式中，vh结构域和vl结构域通常通过使用如本文概述的接头(“scFv接头”)二价附接至单个多肽序列中，这可以是(从N末端开始)vh-接头-vl或vl-接头-vh，通常优选的是前者(包含各侧上的任选结构域接头，这取决于所使用的形式(例如，根据图44))。通常，scFv结构域的C末端附接至第二单体中的铰链的N末端。
如本文所用，“可变区”或“可变结构域”意指包括基本上由分别构成κ、λ和重链免疫球蛋白基因基因座的任何Vκ、Vλ和/或VH基因编码的一个或多个Ig结构域并且含有赋予抗原特异性的CDR的免疫球蛋白的区域。因此，“可变重链结构域”与“可变轻链结构域”配对以形成抗原结合结构域(“ABD”)。另外，每个可变结构域包括从氨基末端到羧基末端按以下顺序布置的三个高变区(“互补决定区”、“CDR”)(可变重链结构域的VHCDR1、VHCDR2和VHCDR3和可变轻链结构域的VLCDR1、VLCDR2和VLCDR3)和四个框架(FR)区：FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4。高变区通常涵盖来自轻链可变区中的约氨基酸残基24-34(LCDR1；“L”表示轻链)、50-56(LCDR2)和89-97(LCDR3)以及重链可变区中的约31-35B(HCDR1；“H”表示重链)、50-65(HCDR2)和95-102(HCDR3)的氨基酸残基；Kabat等人，《免疫学感兴趣的蛋白质序列(SEQUENCES OF PROTEINS OF IMMUNOLOGICAL INTEREST)》，第5版贝塞斯达马里兰州国家卫生研究院公共卫生服务部(Public Health Service,National Institutes ofHealth,Bethesda,Md.)(1991)和/或那些形成高变环的残基(例如轻链可变区中的残基26-32(LCDR1)、50-52(LCDR2)和91-96(LCDR3)以及重链可变区中的26-32(HCDR1)、53-55(HCDR2)和96-101(HCDR3)；Chothia和Lesk(1987)《分子生物学杂志(J.Mol.Biol.)》196:901-917。表2中描述了本发明的特定CDR。
如本文所用，“Fab”或“Fab区”意指包含VH、CH1、VL以及CL免疫球蛋白结构域的多肽，该免疫球蛋白结构域通常位于两条不同的多肽链上(例如VH-CH1位于一条链上而VL-CL位于另一条链上)。Fab可以指分离情况下的这个区或在本文所述的双特异性抗体的背景下的这个区。在Fab的上下文中，除了CH1和CL结构域之外，Fab还包括Fv区。
如本文所使用的，“Fv”或“Fv片段”意指包括ABD的VL和VH结构域的多肽。Fv区可以格式化为Fab(如上文所讨论的，通常是还包含如上文概述的恒定区的两种不同的多肽)和scFv两者，其中VL和VH结构域组合(通常是与如本文所讨论的接头组合)以形成scFv。
本文中的“单链Fv”或“scFv”意指通常使用如本文所讨论的scFv接头来共价附接至可变轻链结构域以形成scFv或scFv结构域的可变重链结构域。scFv结构域由N末端至C末端可呈任一取向(VH-接头-VL或VL-接头-VH)。在序列表和图中所描绘的序列中，VH和VL结构域的顺序在名称中指示，例如，H.X_L.Y意指N末端到C末端是VH-接头-VL，并且L.Y_H.X是VL-接头-VH。然而，任何“H_L”对的公开意味着以任一顺序包括它们。
本文提供的本发明抗体的一些实施方案包括至少一个scFv结构域，该至少一个scFv结构域虽然不是天然发生的但是通常包含通过scFv接头连接在一起的可变重链结构域和可变轻链结构域。如本文所概述，虽然scFv结构域通常由N末端到C末端定向为VH-scFv接头-VL，但是针对任一个scFv结构域(或使用Fab的vh和vl序列构建的那些)，这种定向可以逆向，成为VL-scFv接头-VH，其中取决于形式，任选的接头位于一个末端或两个末端。
本文中的“修饰”意指多肽序列中的氨基酸取代、插入和/或缺失或对与蛋白质化学连接的部分的更改。例如，修饰可以是与蛋白质连接的改变的碳水化合物或PEG结构。本文中的“氨基酸修饰”意指多肽序列中的氨基酸取代、插入和/或缺失。为清楚起见，除非另有说明，否则氨基酸修饰始终是由DNA编码的氨基酸，例如在DNA和RNA中具有密码子的20个氨基酸。
本文中的“氨基酸取代”或“取代”意指用不同的氨基酸替换亲本多肽序列中特定位置的氨基酸。特别地，在一些实施方案中，取代是针对并非天然存在于特定位置、并非天然存在于生物体内或任何生物体内的氨基酸。例如，取代E272Y是指变体多肽，在这一情况下是指Fc变体，其中位置272处的谷氨酸用酪氨酸代替。为了清楚起见，已经被工程化以改变核酸编码序列但不改变起始氨基酸(例如将CGG(编码精氨酸)交换为CGA(仍编码精氨酸)以增加宿主生物表达水平)的蛋白质不是“氨基酸取代”；即，尽管产生了编码相同蛋白质的新基因，但如果蛋白质在其起始的特定位置具有相同氨基酸，则其不是氨基酸取代。
如本文所用，“氨基酸插入”或“插入”意指在亲本多肽序列中的特定位置处添加氨基酸序列。例如，-233E或233E表示在位置233之后和位置234之前插入谷氨酸。另外，-233ADE或A233ADE表示在位置233之后和位置234之前插入AlaAspGlu。
如本文所用，“氨基酸缺失”或“缺失”意指去除亲本多肽序列中特定位置处的氨基酸序列。例如，E233-或E233#、E233()或E233del表示在位置233处的谷氨酸的缺失。另外，EDA233-或EDA233#表示在位置233处开始的序列GluAspAla的缺失。
如本文所用，“变体蛋白质”或“蛋白质变体”或“变体”意指由于至少一个氨基酸修饰而与亲本蛋白质不同的蛋白质。与亲本蛋白质相比，蛋白质变体具有至少一个氨基酸修饰，但并没有多得使得变体蛋白质使用如下所述比对程序将不与亲本蛋白质比对。通常，使用下文所述的比对程序(诸如BLAST)，变体蛋白质(诸如本文概述的变体Fc结构域等)与亲本蛋白质通常至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同。如本文所用，“变体”还指赋予特定功能的特定氨基酸修饰(例如，“异二聚化变体”、“pI变体”、“消融变体”等)。
如下所述，在一些实施方案中，亲本多肽，例如Fc亲本多肽是人野生型序列，诸如来自IgG1、IgG2、IgG3或IgG4的重链恒定结构域或Fc区，但是具有变体的人序列还可以用作“亲本多肽”，例如可以包含美国公开2006/0134105的IgG1/2杂交体。本文的蛋白质变体序列将优选与亲本蛋白序列具有至少约80％的同一性，并且最优选至少约90％的同一性，更优选至少约95％-98％-99％的同一性。因此，如本文所用，“抗体变体”或“变体抗体”意指由于至少一个氨基酸修饰而与亲本抗体不同的抗体，如本文所用，“IgG变体”或“变体IgG”意指由于至少一个氨基酸修饰而与亲本IgG(再次，在许多情况下，来自人IgG序列)不同的抗体，并且如本文所用，“免疫球蛋白变体”或“变体免疫球蛋白”意指由于至少一个氨基酸修饰而与亲本免疫球蛋白序列不同的免疫球蛋白序列。
如本文所用，“Fc变体”或“变体Fc”意指包括Fc结构域中的氨基酸修饰的蛋白质。修饰可以是添加、缺失或取代。Fc变体根据构成其的氨基酸修饰进行定义。因此，例如，N434S或434S是相对于亲本Fc多肽在位置434处具有丝氨酸取代的Fc变体，其中编号是根据EU索引进行的。同样，M428L/N434S定义了相对于亲本Fc多肽具有取代M428L和N434S的Fc变体。WT氨基酸的同一性可能未指明，在此情况下，上述变体被称为428L/434S。应注意，提供取代的顺序是任意的，也就是说，例如428L/434S与434S/428L是相同的Fc变体，以此类推。对于本文所讨论的涉及抗体或其衍生物和片段(例如，Fc结构域)的所有位置，除非另外指出，否则氨基酸位置编号是根据EU索引进行的。“EU索引”或“如Kabat中的EU索引”或“EU编号”方案是指EU抗体的编号(Edelman等人,1969,《美国国家科学院院刊》63:78-85，所述文献在此通过引用整体并入)。
通常，变体Fc结构域与对应的亲本人IgG Fc结构域具有至少约80％、85％、90％、95％、97％、98％或99％同一性(使用下文所讨论的同一性算法，其中一个实施方案利用如本领域已知的BLAST算法，使用默认参数)。可替代地，与亲本Fc结构域相比，变体Fc结构域可以具有1个、2个、3个、4个、5个、6个、7个、8个、9个、10个、11个、12个、13个、14个、15个、16个、11个、12个、13个、14个、15个、16个、17个、18个、19个或20个氨基酸修饰。可替代地，与亲本Fc结构域相比，变体Fc结构域可以具有至多1个、2个、3个、4个、5个、6个、7个、8个、9个、10个、11个、12个、13个、14个、15个、16个、11个、12个、13个、14个、15个、16个、17个、18个、19个或20个氨基酸修饰。另外，如本文所讨论的，本文所述的变体Fc结构域仍然保持与另一个Fc结构域形成二聚体的能力，如使用本文所述已知技术诸如非变性凝胶电泳所测量。
本文的“蛋白质”意指至少两个共价连接的氨基酸，其包含蛋白质、多肽、寡肽和肽。另外，构成本文所述的抗体的多肽可以包含一个或多个侧链或末端的合成衍生化、糖基化、聚乙二醇化、循环变换、环化、其它分子的接头、与蛋白质或蛋白质结构域的融合以及肽标签或标记的添加。
如本文所用，“残基”意指蛋白质中的位置以及其相关的氨基酸同一性。例如，天冬酰胺297(也称为Asn297或N297)是人抗体IgG1中位置297处的残基。
如本文所用，“IgG亚类修饰”或“同种型修饰”意指将一种IgG同种型的一个氨基酸转化为不同比对的IgG同种型中的对应氨基酸的氨基酸修饰。例如，因为在EU位置296处IgG1包含酪氨酸并且IgG2包含苯丙氨酸，所以IgG2中的F296Y取代被认为是IgG亚类修饰。
如本文所用，“非天然发生修饰”意指不是同种型的氨基酸修饰。例如，因为人IgG均不包括位置434处的丝氨酸，因此IgG1、IgG2、IgG3或IgG4(或其杂交体)的取代434S被认为是非天然发生修饰。
如本文所用，“氨基酸”和“氨基酸同一性”意指由DNA和RNA编码的20种天然发生的氨基酸中的一种。
如本文所用，“效应子功能”意指由抗体Fc区与Fc受体或配体的相互作用产生的生物化学事件。效应子功能包括但不限于ADCC、ADCP和CDC。
如本文所用，“IgG Fc配体”意指来自与IgG抗体的Fc区结合以形成Fc/Fc配体复合物的任何生物体的分子，优选多肽。Fc配体包括但不限于FcγRI、FcγRII、FcγRIII、FcRn、C1q、C3、甘露聚糖结合凝集素、甘露糖受体、葡萄球菌蛋白A、链球菌蛋白G和病毒性FcγR。Fc配体还包括Fc受体同源物(FcRH)，其为与FcγR同源的Fc受体家族(Davis等人,2002,《免疫学评论(Immunological Reviews)》190:123-136，其通过引用整体并入)。Fc配体可包括结合Fc的未发现的分子。特定的IgG Fc配体是FcRn和Fcγ受体。如本文所用，“Fc配体”意指来自与抗体的Fc区结合以形成Fc/Fc配体复合物的任何生物体的分子，优选多肽。
如本文所用，“Fcγ受体”或“FcγR”或“FcgammaR”意指与IgG抗体Fc区结合并由FcγR基因编码的蛋白质家族的任何成员。在人类中，该家族包括但不限于FcγRI(CD64)，包括同种型FcγRIa、FcγRIb和FcγRIc；FcγRII(CD32)，包括同种型FcγRIIa(包括同种异型H131和R131)、FcγRIIb(包括FcγRIIb-1和FcγRIIb-2)和FcγRIIc；以及FcγRIII(CD16)，包括同种型FcγRIIIa(包括同种异型V158和F158)和FcγRIIIb(包括同种异型FcγRIIb-NA1和FcγRIIb-NA2)(Jefferis等人，2002,《免疫快报(Immunol Lett)》82:57-65，其通过引用整体并入)，以及任何未发现的人FcγR或FcγR同种型或同种异型。FcγR可以来自任何生物体，包括但不限于人、小鼠、大鼠、兔和猴。小鼠FcγR包括但不限于FcγRI(CD64)、FcγRII(CD32)、FcγRIII(CD16)和FcγRIII-2(CD16-2)以及任何未发现的小鼠FcγR或FcγR同种型或同种异型。
如本文所用，“FcRn”或“新生Fc受体”意指结合IgG抗体Fc区且至少部分地由FcRn基因编码的蛋白质。FcRn可以来自任何生物体，包括但不限于人、小鼠、大鼠、兔和猴。如本领域已知的，功能FcRn蛋白包括两种多肽，通常被称为重链和轻链。轻链是β-2-微球蛋白并且重链由FcRn基因编码。除非本文另有说明，否则FcRn或FcRn蛋白是指FcRn重链与β-2-微球蛋白的复合物。各种FcRn变体用于增加与FcRn受体的结合并且在一些情况下用于增加血清半衰期。“FcRn变体”是增加与FcRn受体的结合的变体，并且合适的FcRn变体在下文中示出。
如本文所用，“亲本多肽”意指随后被修饰以产生变体的起始多肽。亲本多肽可以是天然存在的多肽或者天然存在的多肽的变体或工程化版本。因此，如本文所用，“亲本免疫球蛋白”意指未修饰的免疫球蛋白多肽，其被修饰以产生变体，并且如本文所用，“亲本抗体”意指未修饰的抗体，其被修饰以产生变体抗体。应注意，“亲本抗体”包含如下文概述的已知的市售、以重组方式产生的抗体。在此情形中，“亲本Fc结构域”将是相对于所列举变体；因此，将“变体人IgG1 Fc结构域”与人IgG1的亲本Fc结构域相比较，将“变体人IgG4 Fc结构域”与亲本Fc结构域人IgG4相比较等。
如本文所用，“位置”意指蛋白质序列中的位置。位置可以顺序地编号，或根据确定的形式，例如用于抗体编号的EU索引来编号。
如本文所用，“靶抗原”意指通过包括给定抗体的可变区的抗原结合结构域来特异性地结合的分子。
本文所述的异二聚抗体的单体的下背景通过“链性(strandedness)”意指与“匹配”的两条DNA链相似，将异二聚化变体并入每种单体中以保留“匹配”以形成异二聚体的能力。例如，如果一些pI变体被工程化作为单体A(例如，使pI更高)，则作为也可以利用的“电荷对”的空间变体不干扰pI变体，例如使pI更高的电荷变体被放在同一个“链”或“单体”上以保持两种功能。类似地，对于如以下更全面地概述的以成对的组出现的“偏斜”变体，技术人员将认为pI决定对中的一组将会进入哪个链或单体，从而使得还使用偏斜变体的pI使pI分离最大化。
如本文所用，“靶细胞”意指表达靶抗原的细胞。
在产生根据本文所述的双特异性抗体的上下文中，“宿主细胞”意指含有对双特异性抗体的组分进行编码的外源性核酸并且能够在适合条件下表达双特异性抗体的细胞。下面讨论合适的宿主细胞。
本文中的“野生型或WT”意指在自然界中发现的氨基酸序列或核苷酸序列，包括等位基因变体。WT蛋白具有未经有意修饰的氨基酸序列或核苷酸序列。
本文提供了与人抗体结构域具有序列同一性的多个抗体结构域。两个类似序列(例如，抗体可变结构域)之间的序列同一性可以通过诸如以下文献中的算法测量：Smith,T.F.和Waterman,M.S.(1981)“生物序列的比较(Comparison Of Biosequences)”，《应用数学进展(Adv.Appl.Math.)》2:482[局部同源算法]；Needleman,S.B.和Wunsch,CD.(1970)“可适用于搜索两种蛋白质的氨基酸序列中的类似性的一般方法(A General MethodApplicable To The Search For Similarities In The Amino Acid Sequence Of TwoProteins)”,《分子生物学杂志(J.Mol.Biol.)》48:443[同源比对算法]，Pearson,W.R.和Lipman,D.J.(1988)“用于生物序列比较的改进的工具(Improved Tools For BiologicalSequence Comparison)”，《美国国家科学院院刊(Proc.Natl.Acad.Sci.(U.S.A.))》85:2444[类似性搜索方法]；或Altschul,S.F.等人,(1990)“基本局部比对搜索工具(BasicLocal Alignment Search Tool)”，《分子生物学杂志(J.Mol.Biol.)》215:403-10，“BLAST”算法，参见https://blast.ncbi.nlm.nih.gov/Blast.cgi。当使用前述算法中的任一种时，使用默认参数(用于窗口长度、空位罚分等)。在一个实施方案中，使用默认参数用BLAST算法来完成序列同一性。
本文所述的抗体通常是分离的或重组的。在用于描述本文所公开的各种多肽时，“分离的”意指已经从表达多肽的细胞或细胞培养物中鉴定并且分离和/或回收的多肽。通常，将通过至少一个纯化步骤来制备分离的多肽。“分离的抗体”是指基本上不含具有不同抗原特异性的其它抗体的抗体。“重组”意指在外源性宿主细胞中使用重组核酸技术产生抗体，并且也可以分离抗体。
“特异性结合”或“特异性结合到”特定抗原或表位，或“对”特定抗原或表位“有特异性”意指结合可测量地不同于非特异性相互作用。特异性结合可以例如通过与对照分子的结合相比测定分子的结合来测量，该对照分子通常是不具有结合活性的类似结构的分子。例如，特异性结合可以通过与类似于靶标的对照分子竞争来确定。
针对特定抗原或表位的特异性结合可以例如通过抗体对抗原或表位的KD为至少约10-4M、至少约10-5M、至少约10-6M、至少约10-7M、至少约10-8M、至少约10-9M、替代地至少约10-10M、至少约10-11M、至少约10-12M、或更大来展现，其中KD是指特定抗体-抗原相互作用的解离速率。通常，特异性结合抗原的抗体的KD对于对照分子相对于抗原或表位大20倍、50倍、100倍、500倍、1000倍、5,000倍、10,000倍或更多倍。
而且，特定抗原或表位的特异性结合可以例如通过针对抗原或表位的KA或Ka为以下的抗体来展现：针对相对于对照物的表位大至少20倍、50倍、100倍、500倍、1000倍、5,000倍、10,000倍或更多倍，其中KA或Ka是指特定抗体-抗原相互作用的缔合速率。结合亲和力通常使用Biacore、SPR或BLI测定来测量。
D.本发明的抗体
本发明提供了与人GPC3结合的抗体，包括单克隆抗体和双特异性抗体(应注意，为了便于临床前测试，许多(如果不是大多数的话)示例性抗体也与食蟹猴GPC3结合，但这不是所有实施方案中都需要的)。特别地，提供了结合CD3和GPC3的双特异性抗体，其呈现如下文更全面描述的多种形式。
1.抗体
本文提供的抗体包括不同的抗体结构域，如下文更全面地描述。如本文所述以及所属领域中已知，本文所述的抗体包含重链和轻链内的不同结构域，所述结构域也可以是重叠的。这些结构域包括但不限于Fc结构域、CH1结构域、CH2结构域、CH3结构域、铰链结构域、重链恒定结构域(CH1-铰链-Fc结构域或CH1-铰链-CH2-CH3)、可变重链结构域、可变轻链结构域、轻链恒定结构域、Fab结构域和scFv结构域。
具体地，图15A和15B所描绘的形式是抗体，通常被称为“异二聚抗体”，意指蛋白质具有自组装成异源二聚体Fc结构域中的至少两个相关Fc序列以及至少两个Fv区，无论是作为Fab还是作为scFv。
a.嵌合抗体和人源化抗体
在某些实施方案中，本文所述的抗体包含来自特定种系重链免疫球蛋白基因的重链可变区和/或来自特定种系轻链免疫球蛋白基因的轻链可变区。例如，此类抗体可以包含人类抗体或由人类抗体组成，该人类抗体包含作为特定种系序列“的产物”或“来源于”特定种系序列的重链或轻链可变区。作为人类种系免疫球蛋白序列“的产物”或“来源于”其的人类抗体可以通过将人类抗体的氨基酸序列与人类种系免疫球蛋白的氨基酸序列比较且选择与人类抗体的序列在序列方面最接近(也就是说，最大同一性％)的人类种系免疫球蛋白序列(使用本文所概述的方法)来鉴别出来。由于例如天然存在的体细胞突变或有意引入定点突变，作为特定人类种系免疫球蛋白序列“的产物”或“来源于”特定人类种系免疫球蛋白序列的人类抗体与种系序列相比可含有氨基酸差异。然而，人源化抗体通常与由人类种系免疫球蛋白基因编码的氨基酸序列在氨基酸序列中具有至少90％相同，并且在与其他物种的种系免疫球蛋白氨基酸序列(例如，鼠种系序列)进行比较时，含有将抗体鉴定为来源于人类序列的氨基酸残基。在某些情况下，人源化抗体可以与由种系免疫球蛋白基因编码的氨基酸序列在氨基酸序列中至少95％、96％、97％、98％或99％，或甚至至少96％、97％、98％或99％相同。通常，来源于特定人类种系序列的人源化抗体将显示出与由人类种系免疫球蛋白基因编码的氨基酸序列不多于10个-20个氨基酸差异(在引入本文中的任何偏斜变体、pI变体和消融变体之前；也就是说，在引入本文所述的变体之前，变体的数量通常较低)。在某些情况下，相比于由种系免疫球蛋白基因编码的氨基酸序列，人源化抗体可显示出不超过5或甚至不超过4、3、2或1个氨基酸差异(同样，在引入本文的任何偏斜变体、pI变体和消融变体之前；也就是说，在引入本文所述的变体之前，变体的数量通常较低)。
在一个实施方案中，亲本抗体已经发生亲和力成熟，如本领域中已知。基于结构的方法可用于人源化和亲和力成熟，例如USSN 11/004,590中所述。可以采用基于选择的方法以对抗体可变区进行人源化和/或亲和力成熟，所述方法包含但不限于以下所述的方法：Wu等人，1999,《分子生物学杂志(J.Mol.Biol.)》294:151-162；Baca等人，1997，《生物化学杂志(J.Biol.Chem.)》272(16):10678-10684；Rosok等人，1996，《生物化学杂志》271(37):22611-22618；Rader等人，1998，《美国国家科学院院刊(Proc.Natl.Acad.Sci.USA)》95:8910-8915；Krauss等人，2003，《蛋白质工程化》16(10):753-759，所述文献均通过引用整体并入。其他人源化方法可涉及仅移植部分CDR，包括但不限于以下文献中所述的方法：USSN09/810,510；Tan等人,2002,《免疫学杂志(J.Immunol.)》169:1119-1125；De Pascalis等人，2002，《免疫学杂志》169:3076-3084，所述文献均通过引用并入。
2.异二聚抗体
在例示性实施方案中，本文提供的双特异性抗体是包含两个变异Fc结构域序列的异二聚双特异性抗体。此类变体Fc结构域包含氨基酸修饰以促进异二聚抗体的自组装和/或纯化。
抗体技术中正存在的一个问题是期望“双特异性”抗体同时与两种不同抗原结合，通常由此允许不同抗原接近且从而产生新功能和新疗法。通常，这些抗体是通过将每条重链和轻链的基因纳入宿主细胞中来产生。这通常引起所期望的异二聚体(A-B)以及两种同源二聚体(A-A和B-B(不包含轻链异二聚体问题))的形成。然而，形成双特异性抗体的主要障碍是难以使期望异二聚抗体的形成偏向于同源二聚体的形成和/或难以从同源二聚体抗体中纯化异二聚抗体。
存在多种机制可以用于产生本发明异二聚抗体。另外，如本领域的技术人员将理解的，这些不同的机制可以组合以确保高异二聚化。促进异二聚体的产生和纯化的氨基酸修饰通常统称为“异二聚化变体”。如下文所讨论，异二聚化变体包括“偏斜”变体(例如下文所述的“杵和臼”以及“电荷对”变体)以及“pI变体”，其允许从同源二聚体中纯化异二聚体。如在美国专利号US 9,605,084(其全部内容通过引用并入本文)中一般性描述的，并且特别是如下文对异二聚化变体所讨论，异二聚化的有用机理包括美国专利号US 9,605,084中所述的“杵和臼”(“KIH”)、美国专利号US 9,605,084中所述的“静电转向(electrostaticsteering)”或“电荷对”、美国专利号US 9,605,084中所述的pI变体以及美国专利号US 9,605,084中概述的一般另外的Fc变体及以下内容。
可用于形成和纯化本发明异二聚抗体(例如，双特异性抗体)的异二聚化变体在下文进一步详细讨论。
a.偏斜变体
在一些实施方案中，异二聚抗体包含偏斜变体，该偏斜变体是在第一Fc结构域(A)和/或第二Fc结构域(B)中的一个或多个氨基酸修饰，一个或多个氨基酸修饰有利于形成Fc异二聚体(包含第一Fc结构域和第二Fc结构域的Fc二聚体)；(A-B)超过Fc同源二聚体(包含第一Fc结构域中的两个或第二Fc结构域中的两个的Fc二聚体；A-A或B-B)。合适的偏斜变体包括在美国公开申请号2016/0355608的图29以及图1中，所述美国公开申请在此通过引用整体并入并且具体地并入其对偏斜变体的公开内容。
因此，将允许形成异二聚Fc区的合适的Fc异二聚化变体对在图1中示出。因此，第一Fc结构域具有第一Fc异二聚化变体，并且第二Fc结构域具有选自图1中的对的第二Fc异二聚化变体。
一种机制在本领域中通常称为“杵和臼”，是指也可以任选地使用产生空间影响以利于异二聚体形成和不利于同源二聚体的形成的氨基酸工程；这有时称为“杵和臼”，如USSN 61/596,846，Ridgway等人，《蛋白质工程(Protein Engineering)》9(7):617(1996)；Atwell等人，《分子生物学杂志(J.Mol.Biol.)》1997 270:26；美国专利号8,216,805中所述，所有所述文献据此全文以引用方式并入。图标出了依赖于“杵和臼”的“单体A-单体B”对的数目。另外，如Merchant等人，《自然·生物技术(Nature Biotech)》16:677(1998)中所述，这些“杵和臼”突变可以与二硫键组合以偏斜形成异二聚化。
用于生成异二聚体的另外的机制有时被称为“静电转向”，如Gunasekaran等人，《生物化学杂志(J.Biol.Chem.)》285(25):19637(2010)中所述，所述文献据此全文以引用方式并入。这在本文中有时被称为“电荷对”。在此实施方案中，静电用于使形成偏向异二聚化。如本领域的技术人员将理解的，这些电荷对还可能影响pI并因此影响纯化，并且因此在一些情况下还可以被视为pI变体。然而，由于这些是为了强制发生异二聚化而产生并且不是作为纯化工具使用，因此其被分类为“空间变体”。这些包含但不限于，与D221R/P228R/K409R配对的D221E/P228E/L368E(例如这些是“单体对应组”)和与C220R/E224R/P228R/K409R配对的C220E/P228E/368E。
在一些实施方案中，偏斜变体有利地并且同时有利于基于“杵和臼”机制以及“静电转向”机制两者的异二聚化。在一些实施方案中，异二聚抗体包含一组或多组此类异二聚化偏斜变体。这些变体以成“对”的“组”出现。也就是说，对中的一组并入第一单体中并且该对中的另一组并入第二单体中。应注意，这些组不一定表现为“杵和臼”变体，其中在一个单体上的残基与另一个单体上的残基之间存在一一对应。也就是说，这些成对的组相反可以形成两个单体之间的界面，该界面鼓励异二聚体形成并且不鼓励同源二聚体形成，从而允许在生物学条件下自发形成的异二聚体的百分比超过90％，而非预期的50％(25％同源二聚体A/A:50％异二聚体A/B:25％同源二聚体B/B)。图1中描绘了示例性的异二聚化“偏斜”变体。在示例性实施方案中，异二聚抗体包括Fc异二聚化变体作为组：S364K/E357Q:L368D/K370S；L368D/K370S:S364K；L368E/K370S:S364K；T411T/E360E/Q362E:D401K；L368D/K370S:S364K/E357L；K370S:S364K/E357Q；或T366S/L368A/Y407V:T366W(任选地包括桥接二硫化物、T366S/L368A/Y407V/Y349C:T366W/S354C)都是Fc异二聚化变体的“偏斜”变体氨基酸取代组。在示例性实施方案中，异二聚抗体包含“S364K/E357Q:L368D/K370S”氨基酸取代组。就命名而言，对“S364K/E357Q:L368D/K370S”意指一个单体包括具有氨基酸取代S364K和E357Q的Fc结构域，且另一单体包括具有氨基酸取代L368D和K370S的Fc结构域；如上所述，这些对的“链性”取决于起始pI。
在一些实施方案中，本文提供的偏斜变体可以任选地并且独立地与任何其他修饰——包括但不限于其他偏斜变体(参见例如，美国公开申请号2012/0149876的图37中，所述美国公开申请通过引用并入本文，特别是出于其对偏斜变体的公开的原因而并入)、pI变体、同种型变体、FcRn变体、消融变体等——一起结合到异二聚抗体的第一Fc结构域和第二Fc结构域中的一者或两者中。此外，单个修饰也可以独立地并且任选地包含在本发明异二聚抗体中或从本发明异二聚抗体中排除。
另外的单体A和单体B变异体可以任选地且独立地以任何量与其它变异体(如本文所概述的pI变异体或US2012/0149876的图37中所示的其它空间变异体，其中的图和图例和SEQ ID NO特此并入本文中供参考)组合。
在一些实施方案中，本文所概述的空间变体可以任选且独立地与任何pI变体(或其它变体，如Fc变体、FcRn变体等)并入到一个或两个单体中，并且可以独立且任选地包含在本文所述的抗体的蛋白质中或从本文所述的抗体的蛋白质中排除。
合适的偏斜变体的列表见于图1，示出了在许多实施方案中的一些对的特定用途。包含但不限于以下的成对的组特别用于许多实施方案中：S364K/E357Q:L368D/K370S；L368D/K370S:S364K；L368E/K370S:S364K；T411T/E360E/Q362E:D401K；L368D/K370S:S364K/E357L和K370S:S364K/E357Q。就命名法而言，对“S364K/E357Q:L368D/K370S”意指单体中的一者具有双变体组S364K/E357Q并且另一者具有双变体组L368D/K370S。
b.用于异二聚体的pI(等电点)变体
在一些实施方案中，异二聚抗体包含有利地允许从同源二聚体蛋白质分离异二聚抗体(例如，抗GPC3×抗CD3双特异性抗体)的纯化变体。
存在若干种基本机制可以导致易于纯化异二聚化抗体。例如，对抗体重链单体A和B中的一者或两者的修饰，使得每个单体具有不同的pI，允许从单体A-A和B-B蛋白等电纯化异二聚A-B抗体。可替代地，一些支架形式，如“1+1 Fab-scFv-Fc”和“2+1 Fab2-scFv-Fc”形式，也允许基于大小进行分离。如本文所述，还可能使用偏斜变体，相对于同源二聚体“偏斜”异二聚体的形成。因此，异二聚化偏斜变体和pI变体的组合特别用于本文提供的异二聚抗体中。
另外，如下文更全面地概述的，根据异二聚抗体的形式，可以使用包含在单体的恒定区和/或Fc结构域内的pI变体和/或结构域接头。在一些实施方案中，异二聚抗体包含对于还可以产生pI变化的替代性功能的另外的修饰，诸如Fc、FcRn和KO变体。
在一些实施方案中，本文提供的本发明异二聚抗体包含至少一个单体，该至少一个单体具有改变单体的pI的一个或多个修饰(即，“pI变体”)。通常，如本领域技术人员将了解的，存在两种一般类别的pI变体：增大蛋白质的pI(碱性变化)的变体和减小蛋白质的pI(酸性变化)的变体。如本文所述，可以进行这些变体的所有组合：一种单体可以是野生型，或者不显示与野生型显著不同的pI的变体，并且另一种可以是更碱性或更酸性的。可替代地，改变每种单体，一种具有更强碱性且一种具有更强酸性。
根据异二聚体抗体的形式，pI变体可以包含在单体的恒定结构域和/或Fc结构域内，或者可以使用带电荷的接头，结构域接头或scFv接头。也就是说，利用如“1+1 Fab-scFv-Fc”等一个或多个scFv的抗体形式可以包含出于纯化目的给出另外的pI助推的带电荷的scFv接头(带正电或负电)。如本领域的技术人员将理解的，一些1+1 Fab-scFv-Fc形式可与仅带电荷的scFv接头一起使用而无另外的pI调整，但是本文所述的抗体确实还提供了在单体中的一个或两个上的pI变体和/或带电荷的结构域接头。另外，用于替代性功能的另外的氨基酸工程化还可赋予pI变化，如Fc、FcRn和KO变体。
在将pI用作分离机制以允许纯化异二聚体蛋白的本发明异二聚抗体中，将氨基酸变体引入到单体多肽中的一个或两个单体多肽中。也就是说，所述单体之一(为了简单起见，在本文中被称为“单体A”)的pI可以被工程化为远离单体B，或单体A和单体B两者均可以随着单体A的pI增加和单体B的pI降低而改变。如下文更全面地概述的，任一个或两个单体的pI变化可以通过以下来完成：去除或添加带电荷的残基(例如，用带正电或带负电的氨基酸残基来代替中性氨基酸，例如甘氨酸到谷氨酸)、将带电荷的残基从带正电或带负电改变为相反电荷(例如，天冬氨酸到赖氨酸)或将带电荷的残基改变为中性残基(例如，电荷损失；赖氨酸到丝氨酸)。图1和图2中示出了多种这些变体。
因此，在一些实施方案中，本发明异二聚抗体包含在恒定区中的氨基酸修饰，该氨基酸修饰通过将氨基酸取代(“pI变体”或“pI取代”)结合到单体中的一个或两个中来更改二聚体蛋白的单体中的至少一个(如果不是两个)的等电点(pI)以形成“pI抗体”。如本文所示，如果两种单体的pI差别小至0.1pH单位，则可以实现异源二聚体与两种同型二聚体的分离，其中0.2、0.3、0.4和0.5或更高都可用于本文所述的抗体中。
如本领域的技术人员将理解的，每个或两个单体上要包含的用于得到良好分离的pI变体的数量将部分地取决于组分的起始pI，例如在1+1 Fab-scFv-Fc和2+1 Fab2-scFv-Fc形式中，所关注scFv和Fab的起始pI。即，为了确定对哪个单体进行工程化或处于哪个“方向”(例如，更具阳性或更具阴性)，计算这两种靶抗原的Fv序列并据此作出决定。如本领域已知的，不同的Fv将具有用于本文所述的抗体中的不同起始pI。通常，如本文所概述的，pI被工程化以使各个单体的总pI差为至少约0.1log，如本文所概述的优选的是0.2到0.5。
在pI变体用于实现异二聚化的情况下，通过使用一个或多个重链的一个或多个恒定区，提供了用于设计和纯化双特异性蛋白质(包含抗体)的更模块化方法。因此，在一些实施方案中，异二聚化变体(包含偏斜和pI异二聚化变体)并不包含在可变区中，使得每个单独的抗体必须工程化。另外，在一些实施方案中，通过导入来自不同IgG同种型的pI变体以便在不引入显著免疫原性的情况下改变pI来显著降低pI变体导致免疫原性的可能性。因此，待解决的另一个问题是阐明具有高人类序列含量的低pI恒定结构域，例如最小化或避免任何特定位置的非人类残基。可替代地或除同种型取代外，通过利用同配取代(例如，Asn至Asp；和Gln至Glu)显著降低了pI变体导致免疫原性的可能性。
如下文所论述，可能与这个pI工程化一起发生的负效应同样是血清半衰期延长和FcRn结合增加。也就是说，如在美国公开申请号US 2012/0028304(以引用方式整体并入)中所述，降低抗体恒定结构域(包含在抗体和Fc融合中找到的那些)的pI可能导致血清保留在体内更长时间。这些用于增加血清半衰期的pI变体也促进用于纯化的pI变化。
另外，应注意，pI变体给予了双特异性抗体的分析和质量控制过程另外益处，因为在同源二聚体存在时消除、最小化和区分的能力是显著的。类似地，可靠地测试异二聚抗体产生的再现性的能力是重要的。
通常，特定用途的实施方案依赖于包含偏斜变体的变体组，相比于同源二聚化形成，该偏斜变体与pI变体结合促成异二聚化形成，该pI变体增加两个单体之间的pI差异以促进将异二聚体从同源二聚体中纯化出来。
pI变体的示例性组合示出于美国公开申请号2016/0355608中的图1和图2以及图30中，所有所述文献通过引用整体并入本文，特别是针对pI变体的公开内容并入。图1和图2中示出了pI变体的优选组合。如本文所概述和附图中所示，这些变化相对于IgG1示出，但所有同种型以及同种型杂交体可以按此方式改变。在重链恒定结构域来自IgG2-IgG4的情况下，也可以使用R133E和R133Q。
因此，在一些实施方案中，一个单体具有来自图2的一组取代并且另一个单体具有带电荷的接头(呈带电荷的scFv接头的形式，因为所述单体包括如形式所指示的scFv或带电荷的结构域接头，所述带电荷的结构域接头可以选自图5和图6中所描绘的那些)。
在一些实施方案中，在Fc结构域的铰链中进行修饰，包括基于EU编号的位置216、217、218、219、220、221、222、223、224、225、226、227、228、229和230。因此，pI突变和特别是取代可以在位置216-230中的一个或多个位置中进行，其中可使用1个、2个、3个、4个或5个突变。同样，设想了单独或与其他结构域中的其他pI变体一起的所有可能的组合。
可用于降低铰链结构域的pI的特定取代包括但不限于位置221处的缺失、位置222处的非天然缬氨酸或苏氨酸、位置223处的缺失、位置224处的非天然谷氨酸、位置225处的缺失、位置235处的缺失和位置236处的缺失或非天然丙氨酸。在一些情况下，仅在铰链结构域中进行pI取代，并且在其他情况下，这些取代以任何组合添加到其他结构域中的其他pI变体。
在一些实施方案中，可以在CH2区中进行突变，包括基于EU编号的位置233、234、235、236、274、296、300、309、320、322、326、327、334和339。应该注意，可以进行233-236的改变以增加IgG2主链中的效应子功能(以及327A)。同样，可以对这14个位置进行所有可能的组合；例如可包括具有1个、2个、3个、4个、5个、6个、7个、8个、9个或10个CH2 pI取代的变体Fc结构域。
可用于降低CH2结构域的pI的具体取代包括但不限于位置274处的非天然谷氨酰胺或谷氨酸、位置296处的非天然苯基丙氨酸、位置300处的非天然苯基丙氨酸、位置309处的非天然缬氨酸、位置320处的非天然谷氨酸、位置322处的非天然谷氨酸、位置326处的非天然谷氨酸、位置327处的非天然甘氨酸、位置334处的非天然谷氨酸、位置339处的非天然苏氨酸以及CH2内和与其他结构域的所有可能的组合。
在此实施方案中，修饰可以独立地并且任选地选自CH3区的位置355、359、362、384、389、392、397、418、419、444和447(EU编号)。可用于降低CH3结构域的pI的具体取代包括但不限于位置355处的非天然谷氨酰胺或谷氨酸、位置384处的非天然丝氨酸、位置392处的非天然天冬酰胺或谷氨酸、位置397处的非天然甲硫氨酸、位置419处的非天然谷氨酸、位置359处的非天然谷氨酸、位置362处的非天然谷氨酸、位置389处的非天然谷氨酸、位置418处的非天然谷氨酸、位置444处的非天然谷氨酸，以及位置447处的缺失或非天然天冬氨酸。
通常，如本领域技术人员将了解的，存在两种一般类别的pI变体：增大蛋白质的pI(碱性变化)的变体和减小蛋白质的pI(酸性变化)的变体。如本文所述，可以进行这些变体的所有组合：一种单体可以是野生型，或者不显示与野生型显著不同的pI的变体，并且另一种可以是更碱性或更酸性的。可替代地，改变每种单体，一种具有更强碱性且一种具有更强酸性。
pI变体的优选组合示于图2中。如本文所概述和附图中所示，这些变化相对于IgG1示出，但所有同种型以及同种型杂交体可以按此方式改变。在重链恒定结构域来自IgG2-IgG4的情况下，也可以使用R133E和R133Q。
在一个实施方案中，例如在图15和图44形式中，pI变体的优选组合具有包括208D/295E/384D/418E/421D变体(在相对于人IgG1时是N208D/Q295E/N384D/Q418E/N421D)的一个单体(负Fab侧)和包括带正电的scFv接头的第二单体(正scFv侧)，包含(GKPGS)4(SEQ IDNO:15)。然而，如本领域的技术人员将理解的，第一单体包含CH1结构域，其包含位置208。因此，在不包含CH1结构域的构建体(例如，针对不在所述结构域之一上利用CH1结构域的抗体，例如以双scFv形式或“单臂”形式，诸如图44C或图44D所描绘的形式)中，优选的负pI变体Fc组包含295E/384D/418E/421D变体(在相对于人IgG1时是Q295E/N384D/Q418E/N421D)。
因此，在一些实施方案中，一个单体具有来自图4的一组取代并且另一个单体具有带电荷的接头(呈带电荷的scFv接头的形式，因为该单体包括如形式所指示的scFv或带电荷的结构域接头，该带电荷的结构域接头可以选自图5和图6中所描绘的那些)。
c.同种型变体
另外，本文所述的抗体的许多实施方案依赖于将来自一种IgG同种型的特定位置的pI氨基酸“引进”另一种IgG同种型中，从而减少或排除变体中引入非所需免疫原性的可能性。许多这些示出在美国公开2014/0370013的图21中，所述美国公开特此以引用方式并入。也就是说，出于多种原因，包括高效应子功能，IgG1是治疗性抗体的常见同种型。然而，IgG1的重链恒定区具有比IgG2的重链恒定区更高的pI(8.10相对于7.31)。通过将特定位置的IgG2残基引入IgG1主链中，使得所得单体的pI降低(或提高)且另外展现出较长的血清半衰期。例如，IgG1在位置137处具有甘氨酸(pI 5.97)，并且IgG2具有谷氨酸(pI 3.22)；导入谷氨酸将影响所得蛋白质的pI。如下文所描述的，通常需要多个氨基酸取代来显著影响变体抗体的pI。然而，应注意，如下文所讨论的，即便是IgG2分子发生变化也允许血清半衰期增加。
在其他实施方案中，进行非同种型氨基酸变化，以减少所得蛋白质的总电荷状态(例如通过将更高的pI氨基酸变为更低的pI氨基酸)，或允许在结构中调节稳定性等等，如下文进一步描述。
另外，通过对重链和轻链恒定结构域进行pI工程化，可以发现异二聚体的每个单体中发生显著变化。如本文所讨论的，使两个单体的pI相差至少0.5可以通过离子交换色谱法或等电聚焦或对等电点敏感的其他方法进行分离。
d.计算pI
每个单体的pI可以取决于变体重链恒定结构域的pI和总单体的pI，该总单体包括变体重链恒定结构域和融合配偶体。因此，在一些实施方案中，使用美国公开2014/0370013的图19中的图表，基于变体重链恒定结构域计算pI变化。如本文所讨论的，要工程化哪个单体通常由Fv和支架区的固有pI来决定。可替代地，可以比较每个单体的pI。
e.还赋予更好的FcRn体内结合的pI变体
在pI变体降低单体的pI的情况下，其可具有改善体内血清滞留的附加益处。
虽然仍在审查中，但是据信，Fc区在体内具有较长的半衰期，因为在核内体中以pH6与FcRn的结合螯合了Fc(Ghetie和Ward,1997《今日免疫学(Immunol Today.)》18(12):592-598，所述文献以引用方式整体并入)。随后核内体隔室使Fc再循环到细胞表面。一旦隔室向胞外空间打开，则约7.4的较高pH诱导将Fc释放回到血液中。在小鼠中，Dall'Acqua等人显示了，在pH为6和pH为7.4时具有增加的FcRn结合的Fc突变体实际上具有降低的血清浓度和与野生型Fc相同的半衰期(Dall'Acqua等人，2002,《免疫学杂志》169:5171-5180，所述文献以引用方式整体并入)。Fc对FcRn的亲和力在pH 7.4增强被认为是禁止了Fc释放回到血液中。因此，将增加Fc体内半衰期的Fc突变理想地将增强较低pH下的FcRn结合，同时仍允许Fc在较高pH下释放。在6.0至7.4的pH范围内，氨基酸组胺酸改变了其电荷状态。因此，在Fc/FcRn复合物中的重要位置处找到His残基并不出乎意料。
最近，已经提出，带具有较低等电点的可变区的抗体还可以具有较长的血清半衰期(Igawa等人,2010《蛋白质工程设计与选择(PEDS)》23(5):385-392，所述文献以引用方式整体并入)。然而，对其机制仍知之甚少。而且，可变区因抗体而有所不同。具有降低的pI和延长的半衰期的恒定区变体将会提供更具模块化的方法来提高抗体的药代动力学性质，如本文所描述的。
f.用于另外的功能的另外的Fc变体
除了上文所讨论的异二聚化变体之外，存在出于各种原因可以作出的许多有用的Fc氨基酸修饰，包含但不限于更改与一个或多个FcγR受体的结合、更改与FcRn受体的结合等，如以下所讨论的。
因此，本文提供的抗体(异源二聚以及同源二聚)可以包含具有或不具有本文概述的异二聚化变体(例如，pI变体和空间变体)的此类氨基酸修饰。每组变体可以独立地并且任选地包括任何特定的异二聚体蛋白或排除任何特定的异二聚体蛋白。
(i)FcγR变体
因此，可以进行许多有用的Fc取代以改变与一种或多种FcγR受体的结合。在某些实施方案中，本发明抗体包含更改与一种或多种FcγR受体的结合的修饰(即，“FcγR变体”)。导致结合增加以及结合减少的取代可能是有用的。例如，已知增加与FcγRIIIa的结合通常导致增加的ADCC(抗体依赖性细胞介导的细胞毒性；其中表达FcγR的非特异性细胞毒性细胞识别靶细胞上的结合抗体并且随后引起靶细胞溶解的细胞介导反应)。类似地，在一些情况下，与FcγRIIb(一种抑制性受体)的结合减少也可能是有利的。可用于本文所述的抗体的氨基酸取代包含在美国专利号8,188,321(具体地图41)和美国专利号8,084,582以及美国公开申请号20060235208和20070148170中所列举的氨基酸取代，所有所述美国专利以引用方式整体明确并入本文，特别是针对其中公开的变体明确并入本文。可以使用的特定变体包括但不限于236A、239D、239E、332E、332D、239D/332E、267D、267E、328F、267E/328F、236A/332E、239D/332E/330Y、239D/332E/330L、243A、243L、264A、264V和299T。
另外，如通过引用以其全文合并在此的USSN 12/341,769所具体公开的，存在用于增加与FcRn受体的结合以及增加血清半衰期的另外的Fc取代，包括但不限于：434S、434A、428L、308F、259I、428L/434S、428L/434A、259I/308F、436I/428L、436I或V/434S、436V/428L和259I/308F/428L。此类修饰可以包含在本发明抗体的一个或两个Fc结构域中。
(ii)消融变体
类似地，另一类别的功能变体是“FcγR消融变体”或“Fc敲除(FcKO或KO)”变体。在这些实施方案中，在一些治疗应用中，期望减少或除去Fc结构域与一种或多种或全部Fcγ受体(例如FcγR1、FcγRIIa、FcγRIIb、FcγRIIIa等)的正常结合以避免另外的作用机制。也就是说，例如，在许多实施方案中，特别是在使用与CD3单价地结合的双特异性抗体中，通常期望的是消融FcγRIIIa结合以消除或显著降低ADCC活性。其中一个Fc结构域包含一个或多个Fcγ受体消融变体。图14中描绘了这些消融变体，并且各自可以独立且任选地包含在内或不包含在内，优选方面利用了选自由以下组成的组的消融变体：G236R/L328R、E233P/L234V/L235A/G236del/S239K、E233P/L234V/L235A/G236del/S267K、E233P/L234V/L235A/G236del/S239K/A327G、E233P/L234V/L235A/G236del/S267K/A327G和E233P/L234V/L235A/G236del。应注意本文中提及的消融变体消融FcγR结合，但是通常不消融FcRn结合。
如本领域所已知的，人IgG1的Fc结构域具有与Fcγ受体的最高结合，并且因此，在异二聚抗体的主链中的恒定结构域(或Fc结构域)为IgG1时，可以使用消融变体。例如，可替代地或除了IgG1背景下的消融变体之外，糖基化位置297处的突变(通常突变成A或S)可以显著消融与FcγRIIIa的结合。人IgG2和IgG4具有与Fcγ受体天然减少的结合，并且因此那些主链可以在有或没有消融变体的情况下使用。
E.异二聚变体和Fc变体的组合
如本领域技术人员将理解的，所有异二聚化变体(包括偏斜和/或pI变体)都可以任选地并且独立地以任何方式组合，只要其保留其“链性”或“单体划分”。在一些实施方案中，本文提供的异二聚抗体包括异二聚化偏斜变体、同配pI取代和FcKO变体的组合，如图4所描绘。另外，所有这些变体可以组合成异二聚化形式中的任一种异二聚化形式。
在pI变体的情况下，虽然附图中示出了特别有用的实施方案，但是可以遵循改变两个单体之间的pI差以促进纯化的基本规则，以生成其他组合。
另外，任何异二聚化变体，偏斜和pI，也独立地并且任选地与Fc消融变体、Fc变体、FcRn变体组合，如本文总体概述的。
包含在异二聚体1+1 Fab-scFv-Fc和2+1 Fab2-scFv-Fc形式抗体的一些实施方案中的变体的示例性组合包含在图4中。在某些实施方案中，抗体是异二聚1+1 Fab-scFv-Fc或2+1 Fab2-scFv-Fc形式的抗体，如图15A和图15B所示。
F.抗GPC3×抗CD3双特异性抗体
在另一方面，本文提供了抗GPC3×抗CD3(本文也称为“αGPC3×αCD3”或有时仅称为“GPC3×CD3”)双特异性抗体。此类抗体包括至少一个GPC3结合结构域和至少一个CD3结合结构域。在一些实施方案中，本文提供的双特异性αGPC3×αCD3在表达GPC3的肿瘤部位选择性地进行免疫应答。
应注意，除非本文另有说明，否则名称中抗原列表的顺序并不赋予结构；即GPC3 XCD3 1+1 Fab-scFv-Fc抗体可以具有与GPC3或CD3结合的scFv，尽管在一些情况下，该顺序指定了所示的结构。
如本文中更全面地概述的，ABD的这些组合可以呈如下文概述的各种形式，通常是一个ABD呈Fab形式并且另一个呈scFv形式的组合。用于本文提供的双特异性抗体的例示性形式包括1+1 Fab-scFv-Fc和2+1 Fab2-scFv-Fv形式(参见例如，图15A和图15B)。其他有用的抗体形式包括但不限于“mAb-Fv”、“mAb-scFv”、“中心-Fv”、“单臂scFv-mAb”、“scFv-mAb”、“双scFv”和“三叉”形式的抗体，如图44中所描绘和下文更全面地描述。
另外，通常，ABD中的一个ABD包括如本文概述的在从N末端到C末端的取向上为VH-scFv接头-VL或VL-scFv接头-VH的scFv。根据形式，其它ABD中的一个或两个通常是包括一个蛋白质链上的VH结构域(通常作为重链的组分)和另一个蛋白质链上的VL(通常作为轻链的组分)的Fab。
如本领域的技术人员将理解的，任何一组6个CDR或VH和VL结构域可以呈scFv形式或Fab形式，该形式然后被添加到重恒定结构域和轻恒定结构域，其中重恒定结构域包括变体(包含在CH1结构域以及Fc结构域内)。序列表中含有的scFv序列利用特定带电荷接头，而如本文概述的，可以使用不带电或其它带电接头，包含图5和图6中所描述的那些。
另外，如上文所讨论的，序列表中使用的用于鉴定CDR的编号是Kabat，然而，可以使用不同的编号，该不同的编号将改变如表2所示的CDR的氨基酸序列。
对于本文所列出的所有可变重链结构域和可变轻链结构域，可以制备另外的变体。如本文概述的，在一些实施方案中，一组6个CDR可以具有0个、1个、2个、3个、4个或5个氨基酸修饰(其中氨基酸取代特别有用)以及可变重链结构域和轻链结构域的框架区的变化，只要框架(除CDR之外)保持与选自图1中的美国专利号7,657,380中列出的那些序列的人种系序列至少约80％、85％或90％同一性，所述美国专利的附图和图例通过引用整体并入本文。因此，例如，如本文所描述的相同CDR可以与来自人种系序列的不同框架序列组合，只要框架区保持与选自图1中的美国专利号7,657,380中列出的那些序列的人种系序列至少80％、85％或90％同一性。可替代地，CDR可以具有氨基酸修饰(例如，来自该组的CDR中的1个、2个、3个、4个或5个氨基酸修饰(即，可以对CDR进行修饰，只要该组的6个CDR中的改变的总数小于6个氨基酸修饰，其中CDR的任何组合改变；例如，vlCDR1中可以存在一个变化，vhCDR2中可以存在两个变化，vhCDR3中可以不存在变化等))，以及具有框架区变化，只要框架区保持与选自图1中的美国专利号7,657,380中列出的那些序列的人种系序列至少80％、85％或90％同一性。
如本文所讨论的，本发明异二聚抗体包含两个抗原结合结构域(ABD)，每个结合GPC3或CD3。如本文所概述，这些异二聚抗体可以是双特异性且二价的(例如以图15A中所描绘的形式，每个抗原结合到单个ABD)或双特异性且三价(例如图15B中所描绘，一个抗原结合到单个ABD且另一个抗原结合到两个)。
另外，通常，ABD中的一个ABD包括如本文概述的在从N末端到C末端的取向上为VH-scFv接头-VL或VL-scFv接头-VH的scFv。根据形式，其它ABD中的一个或两个通常是包括一个蛋白质链上的VH结构域(通常作为重链的组分)和另一个蛋白质链上的VL(通常作为轻链的组分)的Fab。
本公开提供了如下概述的多个ABD。如本领域的技术人员将理解的，任何一组6个CDR或VH和VL结构域可以呈scFv形式或Fab形式，该形式然后被添加到重恒定结构域和轻恒定结构域，其中重恒定结构域包括变体(包含在CH1结构域以及Fc结构域内)。序列表中含有的scFv序列利用特定带电荷的接头，而如本文概述的，可以使用不带电荷的或其他带电荷的接头，包含图5中所描述的那些。
另外，如上文所讨论的，序列表中使用的用于鉴定CDR的编号是Kabat，然而，可以使用不同的编号，该不同的编号将改变如表2所示的CDR的氨基酸序列。
对于本文所列出的所有可变重链结构域和可变轻链结构域，可以制备另外的变体。如本文概述的，在一些实施方案中，一组6个CDR可以具有0个、1个、2个、3个、4个或5个氨基酸修饰(其中氨基酸取代特别有用)以及可变重链结构域和轻链结构域的框架区的变化，只要框架(除CDR之外)保持与选自图1中的美国专利号7,657,380中列出的那些序列的人种系序列至少约80％、85％或90％同一性，所述美国专利的附图和图例通过引用整体并入本文。因此，例如，如本文所描述的相同CDR可以与来自人种系序列的不同框架序列组合，只要框架区保持与选自图1中的美国专利号7,657,380中列出的那些序列的人种系序列至少80％、85％或90％同一性。可替代地，CDR可以具有氨基酸修饰(例如，来自该组的CDR中的1个、2个、3个、4个或5个氨基酸修饰(即，可以对CDR进行修饰，只要该组的6个CDR中的改变的总数小于6个氨基酸修饰，其中CDR的任何组合改变；例如，VLCDR1中可以存在一个变化，VHCDR2中可以存在两个变化，VHCDR3中可以不存在变化等))，以及具有框架区变化，只要框架区保持与选自图1中的美国专利号7,657,380中列出的那些序列的人种系序列至少80％、85％或90％同一性。
1.GPC3抗原结合结构域
本文提供了含有与人GPC3结合的抗原结合结构域的单克隆抗体和双特异性抗体。图12和图13中描绘了6个CDR和/或VH和VL结构域的合适组。在一些实施方案中，异二聚抗体是1+1 Fab-scFv-Fc或2+1 Fab2-scFv-Fv形式的抗体(参见例如图15A和图15B)，尽管可以利用下文概述的任何形式。
在一些实施方案中，抗GPC3 ABD具有选自来自VH的vhCDR1、vhCDR2和vhCDR3序列的一组vhCDR，该VH选自由H1、H1、H1.1、H1.2、H1.3和H1.4组成的组，其序列示于图12和图13中。
在一些实施方案中，抗GPC3 ABD的VH结构域选自由H1、H1、H1.1、H1.2、H1.3和H1.4组成的组，其序列示于图12和图13中。
在一些实施方案中，抗GPC3 ABD具有选自来自VL的vlCDR1、vlCDR2和vlCDR3序列的一组vlCDR，该VL选自由L1、L1.1、L1.2、L1.3、L1.4、L1.5、L1.6、L1.7、L1.8、L1.9、L1.10、L1.16、L1.23、L1.29、L1.31.L1.65、L1.66、L1.68、L1.69、L1.70、L1.71、L1.72和L1.73组成的组，其序列示于图12和图13中。
在一些实施方案中，GPC3 ABD的VL选自由L1、L1.1、L1.2、L1.3、L1.4、L1.5、L1.6、L1.7、L1.8、L1.9、L1.10、L1.16、L1.23、L1.29、L1.31.L1.65、L1.66、L1.68、L1.69、L1.70、L1.71、L1.72和L1.73组成的组，其序列示于图12和图13中。
因此，本文包括具有来自选自由以下组成的组的VH/VL对的一组6个CDR(vhCDR1、vhCDR2、vhCDR3、vlCDR1、vlCDR2和vlCDR3)的GPC3 ABD：[GPC3]H1_L1、[GPC3]H1_L1.1、[GPC3]H1_L1.2、[GPC3]H1_L1.3、[GPC3]H1_L1.4、[GPC3]H1_L1.5、[GPC3]H1_L1.6、[GPC3]H1_L1.7、[GPC3]H1_L1.8、[GPC3]H1_L1.9、[GPC3]H1_L1.10、[GPC3]H1_L1.16、[GPC3]H1_L1.23、[GPC3]H1_L1.29、[GPC3]H1_L1.31、[GPC3]H1_L1.65、[GPC3]H1_L1.66、[GPC3]H1_L1.67、[GPC3]H1_L1.68、[GPC3]H1_L1.70、[GPC3]H1_L1.71、[GPC3]H1_L1.72、[GPC3]H1_L1.73、[GPC3]H1.1_L1、[GPC3]H1.1_L1.1、[GPC3]H1.1_L1.2、[GPC3]H1.1_L1.3、[GPC3]H1.1_L1.4、[GPC3]H1.1_L1.5、[GPC3]H1.1_L1.6、[GPC3]H1.1_L1.7、[GPC3]H1.1_L1.8、[GPC3]H1.1_L1.9、[GPC3]H1.1_L1.10、[GPC3]H1.1_L1.16、[GPC3]H1.1_L1.23、[GPC3]H1.1_L1.29、[GPC3]H1.1_L1.31、[GPC3]H1.1_L1.65、[GPC3]H1.1_L1.66、L1.67、[GPC3]H1.1_L1.68、[GPC3]H1.1_L1.70、[GPC3]H1.1_L1.71、[GPC3]H1.1_L1.72、[GPC3]H1.1_L1.73、[GPC3]H1.2_L1、[GPC3]H1.2_L1.1、[GPC3]H1.2_L1.2、[GPC3]H1.2_L1.3、[GPC3]H1.2_L1.4、[GPC3]H1.2_L1.5、[GPC3]H1.2_L1.6、[GPC3]H1.2_L1.7、[GPC3]H1.2_L1.8、[GPC3]H1.2_L1.9、[GPC3]H1.2_L1.10、[GPC3]H1.2_L1.16、[GPC3]H1.2_L1.23、[GPC3]H1.2_L1.29、[GPC3]H1.2_L1.31、[GPC3]H1.2_L1.65、[GPC3]H1.2_L1.66、[GPC3]H1.2_L1.67、[GPC3]H1.2_L1.68、[GPC3]H1.2_L1.70、[GPC3]H1.2_L1.71、[GPC3]H1.2_L1.72、[GPC3]H1.2_L1.73、[GPC3]H1.3_L1、[GPC3]H1.3_L1.1、[GPC3]H1.3_L1.2、[GPC3]H1.3_L1.3、[GPC3]H1.3_L1.4、[GPC3]H1.3_L1.5、[GPC3]H1.3_L1.6、[GPC3]H1.3_L1.7、[GPC3]H1.3_L1.8、[GPC3]H1.3_L1.9、[GPC3]H1.3_L1.10、[GPC3]H1.3_L1.16、[GPC3]H1.3_L1.23、[GPC3]H1.3_L1.29、[GPC3]H1.3_L1.31、[GPC3]H1.3_L1.65、[GPC3]H1.3_L1.66、[GPC3]H1.3_L1.67、[GPC3]H1.3_L1.68、[GPC3]H1.3_L1.70、[GPC3]H1.3_L1.71、[GPC3]H1.3_L1.72、[GPC3]H1.3_L1.73、[GPC3]H1.4_L1、[GPC3]H1.4_L1.1、[GPC3]H1.4_L1.2、[GPC3]H1.4_L1.3、[GPC3]H1.4_L1.4、[GPC3]H1.4_L1.5、[GPC3]H1.4_L1.6、[GPC3]H1.4_L1.7、[GPC3]H1.4_L1.8、[GPC3]H1.4_L1.9、[GPC3]H1.4_L1.10、[GPC3]H1.4_L1.16、[GPC3]H1.4_L1.23、[GPC3]H1.4_L1.29、[GPC3]H1.4_L1.31、[GPC3]H1.4_L1.65、[GPC3]H1.4_L1.66、[GPC3]H1.4_L1.67、[GPC3]H1.4_L1.68、[GPC3]H1.4_L1.70、[GPC3]H1.4_L1.71、[GPC3]H1.4_L1.72和[GPC3]H1.4_L1.73。
另外，本文包括具有选自由以下组成的组的VH/VL对的GPC3 ABD：[GPC3]H1_L1、[GPC3]H1_L1.1、[GPC3]H1_L1.2、[GPC3]H1_L1.3、[GPC3]H1_L1.4、[GPC3]H1_L1.5、[GPC3]H1_L1.6、[GPC3]H1_L1.7、[GPC3]H1_L1.8、[GPC3]H1_L1.9、[GPC3]H1_L1.10、[GPC3]H1_L1.16、[GPC3]H1_L1.23、[GPC3]H1_L1.29、[GPC3]H1_L1.31、[GPC3]H1_L1.65、[GPC3]H1_L1.66、[GPC3]H1_L1.67、[GPC3]H1_L1.68、[GPC3]H1_L1.70、[GPC3]H1_L1.71、[GPC3]H1_L1.72、[GPC3]H1_L1.73、[GPC3]H1.1_L1、[GPC3]H1.1_L1.1、[GPC3]H1.1_L1.2、[GPC3]H1.1_L1.3、[GPC3]H1.1_L1.4、[GPC3]H1.1_L1.5、[GPC3]H1.1_L1.6、[GPC3]H1.1_L1.7、[GPC3]H1.1_L1.8、[GPC3]H1.1_L1.9、[GPC3]H1.1_L1.10、[GPC3]H1.1_L1.16、[GPC3]H1.1_L1.23、[GPC3]H1.1_L1.29、[GPC3]H1.1_L1.31、[GPC3]H1.1_L1.65、[GPC3]H1.1_L1.66、L1.67、[GPC3]H1.1_L1.68、[GPC3]H1.1_L1.70、[GPC3]H1.1_L1.71、[GPC3]H1.1_L1.72、[GPC3]H1.1_L1.73、[GPC3]H1.2_L1、[GPC3]H1.2_L1.1、[GPC3]H1.2_L1.2、[GPC3]H1.2_L1.3、[GPC3]H1.2_L1.4、[GPC3]H1.2_L1.5、[GPC3]H1.2_L1.6、[GPC3]H1.2_L1.7、[GPC3]H1.2_L1.8、[GPC3]H1.2_L1.9、[GPC3]H1.2_L1.10、[GPC3]H1.2_L1.16、[GPC3]H1.2_L1.23、[GPC3]H1.2_L1.29、[GPC3]H1.2_L1.31、[GPC3]H1.2_L1.65、[GPC3]H1.2_L1.66、[GPC3]H1.2_L1.67、[GPC3]H1.2_L1.68、[GPC3]H1.2_L1.70、[GPC3]H1.2_L1.71、[GPC3]H1.2_L1.72、[GPC3]H1.2_L1.73、[GPC3]H1.3_L1、[GPC3]H1.3_L1.1、[GPC3]H1.3_L1.2、[GPC3]H1.3_L1.3、[GPC3]H1.3_L1.4、[GPC3]H1.3_L1.5、[GPC3]H1.3_L1.6、[GPC3]H1.3_L1.7、[GPC3]H1.3_L1.8、[GPC3]H1.3_L1.9、[GPC3]H1.3_L1.10、[GPC3]H1.3_L1.16、[GPC3]H1.3_L1.23、[GPC3]H1.3_L1.29、[GPC3]H1.3_L1.31、[GPC3]H1.3_L1.65、[GPC3]H1.3_L1.66、[GPC3]H1.3_L1.67、[GPC3]H1.3_L1.68、[GPC3]H1.3_L1.70、[GPC3]H1.3_L1.71、[GPC3]H1.3_L1.72、[GPC3]H1.3_L1.73、[GPC3]H1.4_L1、[GPC3]H1.4_L1.1、[GPC3]H1.4_L1.2、[GPC3]H1.4_L1.3、[GPC3]H1.4_L1.4、[GPC3]H1.4_L1.5、[GPC3]H1.4_L1.6、[GPC3]H1.4_L1.7、[GPC3]H1.4_L1.8、[GPC3]H1.4_L1.9、[GPC3]H1.4_L1.10、[GPC3]H1.4_L1.16、[GPC3]H1.4_L1.23、[GPC3]H1.4_L1.29、[GPC3]H1.4_L1.31、[GPC3]H1.4_L1.65、[GPC3]H1.4_L1.66、[GPC3]H1.4_L1.67、[GPC3]H1.4_L1.68、[GPC3]H1.4_L1.70、[GPC3]H1.4_L1.71、[GPC3]H1.4_L1.72和[GPC3]H1.4_L1.73。
在特定实施方案中，VH/VL对选自由[GPC3]H1.1_L1.16和[GPC3]H1.1_L1.69组成的组。
在特定实施方案中，VH/VL对是Fab并且选自由[GPC3]H1.1_L1.16和[GPC3]H1.1_L1.69组成的组。
如本领域的技术人员将理解的，合适的GPC3结合结构域可以包括如在附图中所描绘的或如其被加下划线的一组6个CDR，或在如本文所述并且如表2中所示的使用不同编号方案的情况下，使用在图12和图13中所描绘的那些序列的VH和VL序列内的其他比对鉴定的CDR。适合的ABD还可以包含如这些序列和附图中所描绘的用作scFv或Fab的整个VH和VL序列。在本文中含有Fv到GPC3的许多实施方案中，结合GPC3的是Fab单体。
除了在附图和序列表中所公开的形成ABD到GPC3的亲本CDR组之外，本文提供了具有包含本文(例如，图12和图13以及序列表)公开的GPC3 ABD CDR的至少一个修饰的CDR的变体GPC3 ABD。在一个实施方案中，与如本文(包括附图和序列表)所述的GPC3结合结构域VH/VL对的6个CDR相比，本发明异二聚抗体的GPC3 ABD包含具有1个、2个、3个、4个、5个、6个、7个、8个、9个、10个氨基酸修饰的一组6个CDR。在示例性实施方案中，与以下GPC3结合结构域[GPC3]H1.1_L1.16和[GPC3]H1.1_L1.69中的一者的6个CDR相比，本发明异二聚抗体的GPC3ABD包含具有1个、2个、3个、4个、5个、6个、7个、8个、9个、10个氨基酸修饰的一组6个CDR。在某些实施方案中，如通过Biacore、表面等离振子共振(SPR)、BLI(生物层干涉法，例如八位位组测定)测定和/或流式细胞术中的至少一者测量，本发明抗体的GPC3 ABD能够结合GPC3，后一种测定在许多实施方案中有特定用途。在特定实施方案中，GPC3 ABD能够结合人GPC3(参见图11)。在一些情况下，每个变体CDR具有不超过1个或2个氨基酸变化，每个CDR不超过1个是特别有用的。
在一些实施方案中，本发明抗体的GPC3 ABD包含与如本文(包括附图和序列表)所述的GPC3 ABD的6个CDR至少90％、95％、97％、98％或99％相同的6个CDR。在示例性实施方案中，本发明抗体的GPC3 ABD包含与以下GPC3结合结构域VH/VL对中的一者的6个CDR至少90％、95％、97％、98％或99％相同的6个CDR：[GPC3]H1.1_L1.16和[GPC3]H1.1_L1.69。在某些实施方案中，如通过Biacore、表面等离振子共振(SPR)、BLI(生物层干涉法，例如八位位组测定)测定和/或流式细胞术中的至少一者测量，本发明抗体的GPC3 ABD能够结合GPC3。在特定实施方案中，GPC3 ABD能够结合人GPC3抗原(参见图11)。
在另一个示例性实施方案中，本发明抗体的GPC3 ABD包含本文(包括附图和序列表(例如，图12和图13))所述的GPC3结合结构域VH/VL对中的任一者的可变重链(VH)结构域和可变轻链(VL)结构域。
在一些实施方案中，本发明抗体包括GPC3 ABD，其包括作为本文公开的GPC3 ABDVH和VL结构域的变体的可变重链结构域和/或可变轻链结构域。在一个实施方案中，变体VH结构域和/或VL结构域与本文(包括附图和序列表)所述的GPC3 ABD的VH和/或VL结构域相比具有1个、2个、3个、4个、5个、6个、7个、8个、9个或10个氨基酸变化。在示例性实施方案中，变体VH结构域和/或VL结构域与以下GPC3结合结构域VH/VL对中的一者的VH和/或VL结构域相比具有1个、2个、3个、4个、5个、6个、7个、8个、9个或10个氨基酸变化：[GPC3]H1.1_L1.16和[GPC3]H1.1_L1.69。在一些实施方案中，该变化在图12和图13中描绘的VH结构域中。在一些实施方案中，该变化在图12和图13中描绘的VL结构域中。在一些实施方案中，该变化在图12和图13中描绘的VH和VL结构域中。在一些实施方案中，一个或多个氨基酸变化在VH和/或VL框架区(FR1、FR2、FR3和/或FR4)中。在一些实施方案中，一个或多个氨基酸变化在一个或多个CDR中。在某些实施方案中，如通过Biacore、表面等离振子共振(SPR)、BLI(生物层干涉法，例如八位位组测定)测定和/或流式细胞术中的至少一者测量，本发明抗体的GPC3 ABD能够结合GPC3。在特定实施方案中，GPC3 ABD能够结合人GPC3抗原(参见图11)。
在一个实施方案中，变体VH和/或VL结构域与如本文(包括附图和序列表)所述的GPC3 ABD的VH和/或VL至少90％、95％、97％、98％或99％相同。在示例性实施方案中，变体VH和/或VL结构域与以下GPC3结合结构域VH/VL对中的一者的VH和/或VL至少90％、95％、97％、98％或99％相同：[GPC3]H1.1_L1.16和[GPC3]H1.1_L1.69。在一些实施方案中，GPC3ABD包含与图12和图13中描绘的VH结构域至少90％、95％、97％、98％或99％相同的VH。在一些实施方案中，GPC3 ABD包含与图12和图13中描绘的VL结构域至少90％、95％、97％、98％或99％相同的VL。在一些实施方案中，GPC3 ABD包含与图12和图13中描绘的VH结构域和VL结构域至少90％、95％、97％、98％或99％相同的VH和VL。在某些实施方案中，如通过Biacore、表面等离振子共振(SPR)、BLI(生物层干涉法，例如八位位组测定)测定和/或流式细胞术中的至少一者测量，本发明抗体的GPC3 ABD能够结合GPC3。在特定实施方案中，GPC3ABD能够结合人GPC3抗原(参见图11)。
2.CD3抗原结合结构域
本发明的异二聚双特异性(例如，抗GPC3×抗CD3抗体)还包含与人εCD3(CD3ε)结合的ABD。
图10中描绘了合适的多组6个CDR和/或VH和VL结构域以及scFv序列。特别使用的CD3结合结构域序列包括但不限于抗CD3 H1.30_L1.47、抗CD3 H1.32_L1.47、抗CD3 H1.89_L1.47、抗CD3 H1.90_L1.47、抗CD3 H1.33_L1.47、抗CD3 H1.31_L1.47、抗CD3 L1.47_H1.30、抗CD3 L1.47_H1.30、抗CD3 L1.47_H1.32、抗CD3 L1.47_H1.89、抗CD3 L1.47_H1.90、抗CD3 L1.47_H1.33和抗CD3 L1.47_H1.31，如图10所描绘。如图10中所示，当抗CD3ABD是scFv结构域时，VH和VL结构域可以呈任一取向。
如本领域的技术人员将理解的，合适的CD3结合结构域可以包括如在图10中所描绘的或如其被加下划线的一组6个CDR，或在如本文所述并且如表2中所示的使用不同编号方案的情况下，使用在图10A至图10F中所描绘的那些序列的VH和VL序列内的其他比对鉴定的CDR。适合的ABD还可以包含如这些序列和附图中所描绘的用作scFv或Fab的整个VH和VL序列。在本文中含有Fv到CD3的许多实施方案中，结合CD3的是scFv单体。
除了在附图和序列表中所公开的形成ABD到CD3的亲本CDR组之外，本文提供了具有包含本文(例如，图10和序列表)公开的CD3 ABD CDR的至少一个修饰的CDR的变体CD3ABDS。在一个实施方案中，与本文(包括附图和序列表)所述的CD3 ABD的6个CDR相比，本发明异二聚抗体(例如，抗GPC3×抗CD3抗体)的CD3 ABD包含具有1个、2个、3个、4个、5个、6个、7个、8个、9个、10个氨基酸修饰的一组6个CDR。在示例性实施方案中，与以下CD3结合结构域中的一者的6个CDR相比，本发明异二聚抗体的CD3 ABD包含具有1个、2个、3个、4个、5个、6个、7个、8个、9个、10个氨基酸修饰的一组6个CDR：抗CD3 H1.30_L1.47、抗CD3 H1.32_L1.47、抗CD3 H1.89_L1.47、抗CD3 H1.90_L1.47、抗CD3 H1.33_L1.47、抗CD3 H1.31_L1.47、抗CD3 L1.47_H1.30、抗CD3 L1.47_H1.30、抗CD3 L1.47_H1.32、抗CD3 L1.47_H1.89、抗CD3 L1.47_H1.90、抗CD3 L1.47_H1.33和抗CD3 L1.47_H1.31(图10)。在某些实施方案中，如通过Biacore、表面等离振子共振(SPR)、流式细胞术和/或BLI(生物层干涉法，例如八位位组测定)测定中的至少一者测量，本发明抗体的CD3 ABD能够结合CD3抗原，后一种测定在许多实施方案中有特定用途。在特定实施方案中，CD3ABD能够结合人CD3。
在一些实施方案中，本发明抗体的CD3 ABD包含与如本文(包括附图和序列表)所述的CD3 ABD的6个CDR至少90％、95％、97％、98％或99％相同的6个CDR。在示例性实施方案中，本发明抗体的CD3 ABD包含与以下CD3结合结构域中的一者的6个CDR至少90％、95％、97％、98％或99％相同的6个CDR：抗CD3 H1.30_L1.47、抗CD3 H1.32_L1.47、抗CD3 H1.89_L1.47、抗CD3 H1.90_L1.47、抗CD3 H1.33_L1.47、抗CD3 H1.31_L1.47、抗CD3 L1.47_H1.30、抗CD3 L1.47_H1.30、抗CD3 L1.47_H1.32、抗CD3 L1.47_H1.89、抗CD3 L1.47_H1.90、抗CD3 L1.47_H1.33和抗CD3 L1.47_H1.31(图10)。在某些实施方案中，如通过Biacore、表面等离振子共振(SPR)、流式细胞术和/或BLI(生物层干涉法，例如八位位组测定)测定中的至少一者测量，CD3 ABD能够结合CD3，后一种测定在许多实施方案中有特定用途。在特定实施方案中，CD3 ABD能够结合人CD3抗原。
在另一个示例性实施方案中，本发明抗体的CD3 ABD包含本文(包括附图和序列表)所述的CD3结合结构域中的任一者的可变重链(VH)结构域和可变轻链(VL)结构域。
在一些实施方案中，本发明抗体包括CD3 ABD，其包括作为本文公开的CD3 ABD VH和VL结构域的变体的可变重链结构域和/或可变轻链结构域。在一个实施方案中，变体VH结构域和/或VL结构域与本文(包括附图和序列表)所述的CD3 ABD的VH和/或VL结构域相比具有1个、2个、3个、4个、5个、6个、7个、8个、9个或10个氨基酸变化。在示例性实施方案中，变体VH结构域和/或VL结构域与以下CD3结合结构域中的一者的VH和/或VL结构域具有1个、2个、3个、4个、5个、6个、7个、8个、9个或10个氨基酸变化：抗CD3 H1.30_L1.47、抗CD3 H1.32_L1.47、抗CD3 H1.89_L1.47、抗CD3 H1.90_L1.47、抗CD3 H1.33_L1.47、抗CD3 H1.31_L1.47、抗CD3 L1.47_H1.30、抗CD3 L1.47_H1.30、抗CD3 L1.47_H1.32、抗CD3 L1.47_H1.89、抗CD3 L1.47_H1.90、抗CD3 L1.47_H1.33和抗CD3 L1.47_H1.31(图10)。在一些实施方案中，该变化在图10中描绘的VH结构域中。在一些实施方案中，该变化在图10中描绘的VL结构域中。在一些实施方案中，该变化在图10中描绘的VH和VL结构域中。在一些实施方案中，一个或多个氨基酸变化在VH和/或VL框架区(FR1、FR2、FR3和/或FR4)中。在一些实施方案中，一个或多个氨基酸变化在一个或多个CDR中。在某些实施方案中，如通过Biacore、表面等离振子共振(SPR)、流式细胞术和/或BLI(生物层干涉法，例如八位位组测定)测定中的至少一者测量，本发明抗体的CD3 ABD能够结合CD3，后一种测定在许多实施方案中有特定用途。在特定实施方案中，CD3 ABD能够结合人CD3抗原。
在一个实施方案中，变体VH和/或VL结构域与如本文(包括附图和序列表)所述的CD3 ABD的VH和/或VL至少90％、95％、97％、98％或99％相同。在示例性实施方案中，变体VH和/或VL结构域与以下CD3结合结构域中的一者的VH和/或VL至少90％、95％、97％、98％或99％相同：抗CD3 H1.30_L1.47、抗CD3 H1.32_L1.47、抗CD3 H1.89_L1.47、抗CD3 H1.90_L1.47、抗CD3 H1.33_L1.47、抗CD3 H1.31_L1.47、抗CD3 L1.47_H1.30、抗CD3 L1.47_H1.30、抗CD3 L1.47_H1.32、抗CD3 L1.47_H1.89、抗CD3 L1.47_H1.90、抗CD3 L1.47_H1.33和抗CD3 L1.47_H1.31(图10)。在一些实施方案中，CD3 ABD包含与图10中描绘的VH结构域至少90％、95％、97％、98％或99％相同的VH。在一些实施方案中，CD3 ABD包含与图10中描绘的VL结构域至少90％、95％、97％、98％或99％相同的VL。在一些实施方案中，CD3 ABD包含与图10中描绘的VH结构域和VL结构域至少90％、95％、97％、98％或99％相同的VH和VL。在某些实施方案中，如通过Biacore、表面等离振子共振(SPR)、流式细胞术和/或BLI(生物层干涉法，例如八位位组测定)测定中的至少一者测量，CD3 ABD能够结合CD3，后一种测定在许多实施方案中有特定用途。在特定实施方案中，CD3 ABD能够结合人CD3抗原。
除了图10的αCD3 ABD之外，用于本发明的另外的ABD包含在WO2014/145806的图14和图15中描绘的那些，所述文献特此整体明确并入本文(包括其中的附图和图例)。
3.接头
如本文所示，存在可以用于共价附接所列举结构域(例如，scFv、Fab、Fc结构域等)的多个合适的接头(用于用作结构域接头或scFv接头)，包含通过重组技术产生的传统肽键。图6中描绘了使本发明抗体的结构域彼此附接的示例性接头。在一些实施方案中，接头肽可以主要包含以下氨基酸残基：Gly、Ser、Ala或Thr。接头肽应当具有足够以确保相对于彼此的正确构象以使得其保留期望活性的方式连接两个分子的长度。在一个实施方案中，接头具有约1个至50个氨基酸的长度，优选约1个至30个氨基酸的长度。在一个实施方案中，可使用长度为1个至20个氨基酸的接头，在一些实施方案中使用约5个至约10个氨基酸。有用的接头包括甘氨酸-丝氨酸聚合物，包括例如(GS)n、(GSGGS)n(SEQ ID NO:3)、(GGGGS)n(SEQ ID NO:2)和(GGGS)n(SEQ ID NO:4)，其中n是至少一(通常为3至4)的整数；甘氨酸-丙氨酸聚合物；丙氨酸-丝氨酸聚合物和其他柔性接头，它们中的一些在图5和图6中示出。可替代地，多种非蛋白质聚合物，包括但不限于聚乙二醇(PEG)、聚丙二醇、聚环氧烷或聚乙二醇和聚丙二醇的共聚物可以用作接头。
其他接头序列可以包括CL/CH1结构域的任何长度的任何序列，但不包括CL/CH1结构域的所有残基；例如CL/CH1结构域的前5个-12个氨基酸残基。接头可以来源于免疫球蛋白轻链，例如Cκ或Cλ。接头可以来源于任何同种型的免疫球蛋白重链，包括例如Cγ1、Cγ2、Cγ3、Cγ4、Cα1、Cα2、Cδ、Cε和Cμ。接头序列还可以来源于其他蛋白质，诸如Ig样蛋白(例如，TCR、FcR、KIR)、铰链区来源的序列以及来自其他蛋白质的其他天然序列。
在一些实施方案中，接头是“结构域接头”，其用于将如本文所概述的任何两个结构域连接在一起。例如，在图15B中，可以存在将Fab的CH1结构域的C末端与scFv的N末端连接的结构域接头，其中另一个任选的结构域接头将scFv的C末端与CH2结构域连接(但是在许多实施方案中，铰链用作此结构域接头)。虽然可以使用任何合适的接头，但许多实施方案利用甘氨酸-丝氨酸聚合物作为结构域接头，包括例如(GS)n、(GSGGS)n(SEQ ID NO:3)、(GGGGS)n(SEQ ID NO:2)和(GGGS)n(SEQ ID NO:4)，其中n是至少一(并且通常为3至4至5)的整数以及允许具有足够的长度和柔性的两个结构域重组连接的任何肽序列以允许每个结构域保留其生物学功能。在一些情况下，并且注意“链性”，如下所概述，可以使用如在scFv接头的一些实施方案中使用的带电荷的结构域接头。图6中描绘了例示性有用的结构域接头。
特别参考用于以“2+1”形式将scFv结构域附接至Fc结构域的结构域接头，有几种具有特殊用途的结构域接头，包括如图6所示的“全铰链C220S变体”、“柔性半铰链”、“带电荷的半铰链1”和“带电荷的半铰链2”。
在一些实施方案中，接头是“scFv接头”，其用于共价附接如本文所讨论的VH和VL结构域。在许多情况下，scFv接头是带电荷的scFv接头，多个该带电荷的scFv接头示出在图5中。因此，在一些实施方案中，本文所述的抗体还提供带电荷的scFv接头，以促进第一单体与第二单体之间的pI分离。也就是说，通过并入带正电荷或负电荷(或在使用不同单体上的scFv的支架的情况下两者皆有)的带电荷的scFv接头，这允许包括带电荷的接头的单体更改pI而不对Fc结构域做出进一步改变。这些带电荷的接头可以被取代到含有标准接头的任何scFv中。再次，如本领域的技术人员将理解的，根据期望的pI变化，带电荷的scFv接头用在正确的“链”或单体上。例如，如本文所讨论的，为了形成1+1 Fab-scFv-Fc形式的异二聚抗体，计算每个期望抗原结合结构域的Fv区的原始pI，并且一个被选择成形成scFv，并且根据pI，选择正或负接头。
带电荷的结构域接头还可以用于增加本文所述的抗体的单体的pI分离，并且因此图5中所包含的那些在本文中可以用于利用接头的任何实施方案中。
G.本发明的有用形式
如本领域的技术人员将理解的并且如下文更全面地讨论的，本文提供的异二聚双特异性抗体可以采取各种构形，如图15以及图44中总体上描绘的。一些附图描绘了“单端”构形，其中分子的一个“臂”上有一种类型的特异性并且另一个“臂”上有不同的特异性。其他附图描绘了“双端”构形，其中分子的“顶部”有至少一种类型的特异性并且分子的“底部”有一种或多种不同的特异性。因此，在一些实施方案中，本文所述的抗体针对共接合不同的第一抗原和第二抗原的新型免疫球蛋白组合物。
如本领域的技术人员将理解的，本文所述的异二聚形式可以具有不同的化合价并且可以是双特异性的。也就是说，本文所述抗体的异二聚抗体可以是二价的和双特异性的，其中一个靶肿瘤抗原(例如，CD3)由一个结合结构域结合并且另一个靶肿瘤抗原(例如，GPC3)由第二结合结构域结合。异二聚抗体还可以是三价的和双特异性的，其中第一抗原由两个结合结构域结合并且第二抗原由第二结合结构域结合。如本文概述的，当CD3是靶抗原之一时，优选的是CD3仅单价地结合，以减少潜在的副作用。
本文所述的抗体利用抗CD3抗原结合结构域与抗GPC3结合结构域的组合。如本领域的技术人员将理解的，可以使用如在任何图中所描绘的抗CD3 CDR、抗CD3可变轻链和可变重链结构域、Fab和scFv的任何集合。类似地，可以使用任何抗GPC3抗原结合结构域，无论是否可以使用如在任何附图中所描绘的CDR、可变轻链结构域和可变重链结构域、Fab和scFv，任选地并且独立地以任何组合进行组合。
1. 1+1 Fab-scFv-Fc形式
发现尤其用于本文所述的抗体中的一种异二聚支架是“1+1 Fab-scFv-Fc”或“开瓶器”形式，如图15A所示，具有CD3结合结构域和肿瘤靶抗原(GPC3)结合结构域的示例性组合。在该实施方案中，抗体的一个重链单体含有单链Fv(“scFv”，如下定义)和Fc结构域。scFv包含可变重链结构域(VH1)和可变轻链结构域(VL1)，其中VH1使用可带电荷的scFv接头附接至VL1(参见例如图5)。scFv使用结构域接头附接至重链(参见例如，图6)。另一个重链单体是“常规”重链(VH-CH1-铰链-CH2-CH3)。1+1 Fab-scFv-Fc还包含与VH-CH1相互作用形成Fab的轻链。此结构在本文中有时被称为“开瓶器”形式，这是由于与开瓶器具有大致视觉相似度。通过使用恒定区(例如，Fc结构域、CH1结构域和/或铰链区)中的如下文更全面地描述的促进异二聚抗体形成的氨基酸变体(例如，上文所讨论的异二聚化变体)，这两个重链单体被放在一起。
本发明的“1+1 Fab-scFv-Fc”形式具有若干个明显优势。如本领域所已知的，依赖于两个scFv构建体的抗体类似物常常具有稳定性和聚合问题，在本文所述的抗体中可以通过添加“常规”的重链和轻链配对来缓解所述稳定性和聚合问题。另外，与依赖于两条重链和两条轻链的形式相反，不存在重链和轻链配对不当(例如重链1与轻链2配对等)的问题。
本文概述的许多实施方案通常依赖于包括第一单体的1+1 Fab-scFv-Fc或“开瓶器”形式抗体，该第一单体包括scFv，该scFv包括使用scFv接头(在许多但并非所有情况下，带电)进行共价附接的可变重链结构域和可变轻链结构域，其中scFv通常通过结构域接头共价附接至第一Fc结构域的N末端。结构域接头可以是带电荷的或不带电荷的以及外源的或内源的(例如，天然铰链结构域的全部或部分)。可以使用任何合适的接头将scFv附接至第一Fc结构域的N末端。在一些实施方案中，结构域接头选自图6中的结构域接头。1+1 Fab-scFv-Fc形式或“开瓶器”形式的第二单体是重链，并且组合物还包含轻链。
通常，在许多优选的实施方案中，scFv是与CD3结合的结构域，并且Fab形成GPC3结合结构域。在图15A中描绘了1+1 Fab-scFv-Fc形式的示例性抗GPC3×抗CD3双特异性抗体。图16和图17中描绘了1+1 Fab-scFv-Fc形式的示例性抗GPC3×抗CD3双特异性抗体。
另外，本文所述抗体的Fc结构域通常包括偏斜变体(例如，如图1所示的一组氨基酸取代，其中特别有用的偏斜变体选自由以下组成的组：S364K/E357Q:L368D/K370S；L368D/K370S:S364K；L368E/K370S:S364K；T411T/E360E/Q362E:D401K；L368D/K370S:S364K/E357L；K370S:S364K/E357Q；T366S/L368A/Y407V:T366W和T366S/L368A/Y407V/Y349C:T366W/S354C)、任选的消融变体(包括图3中示出的那些)、任选的带电荷的scFv接头(包括图5中示出的那些)，并且重链包含pI变体(包括图2中示出的那些)。
在某些实施方案中，1+1 Fab-scFv-Fc支架形式包含第一单体，所述第一单体包含scFv-结构域接头-CH2-CH3单体；第二单体，所述第二单体包含第一可变重链结构域-CH1-铰链-CH2-CH3单体；以及第三单体，所述第三单体包含第一可变轻链结构域。在一些实施方案中，第一单体的CH2-CH3是第一变体Fc结构域，并且第二单体的CH2-CH3是第二变体Fc结构域。在一些实施方案中，scFv包含形成CD3结合部分的scFv可变重链结构域和scFv可变轻链结构域。在某些实施方案中，scFv可变重链结构域和scFv可变轻结构域使用scFv接头(带电，在许多但不是所有情况下)进行共价连接。参见，例如，图5)。在一些实施方案中，第一可变重链结构域和第一可变轻链结构域形成GPC3结合结构域。
在一些实施方案中，1+1 Fab-scFv-Fc形式包含偏斜变体、pI变体和消融变体。因此，一些实施方案包括1+1 Fab-scFv-Fc形式，其包含：a)第一单体(“scFv单体”)，该第一单体包含带电荷的scFv接头(在一些实施方案中，图5的+H序列是优选的)、偏斜变体S364K/E357Q、消融变体E233P/L234V/L235A/G236del/S267K和与如本文概述的CD3结合的scFv；b)第二单体(“Fab单体”)，该第二单体包含偏斜变体L368D/K370S、pI变体N208D/Q295E/N384D/Q418E/N421D、消融变体E233P/L234V/L235A/G236del/S267K和可变重链结构域；和c)轻链，该轻链包含可变轻链结构域(VL)和恒定轻链结构域(CL)，其中编号是根据EU编号进行的。可变重链结构域和可变轻链结构域构成GPC3结合部分。
任何合适的CD3 ABD可包含在1+1 Fab-scFv-Fc形式抗体中，包括本文提供的那些。尤其用于这些实施方案中的CD3结合结构域序列包括但不限于H1.30_L1.47、H1.32_L1.47、H1.89_L1.47、H1.90_L1.47、H1.33_L1.47、H1.31_L1.47、L1.47_H1.30、L1.47_H1.30、L1.47_H1.32、L1.47_H1.89、L1.47_H1.90、L1.47_H1.33和L1.47_H1.31或它们的变体，以及在WO2014/145806的图10中描绘的那些以及图14和图15中描绘的那些，所述文献特此通过引用并入(包括图例)。
任何合适的GPC3 ABD可包含在1+1 Fab-scFv-Fc形式抗体中，包括本文提供的那些。在这些实施方案中特别有用的GPC3 ABD包括但不限于选自具有选自由以下组成的组的VH/VL对的VH和VL结构域：[GPC3]H1_L1、[GPC3]H1_L1.1、[GPC3]H1_L1.2、[GPC3]H1_L1.3、[GPC3]H1_L1.4、[GPC3]H1_L1.5、[GPC3]H1_L1.6、[GPC3]H1_L1.7、[GPC3]H1_L1.8、[GPC3]H1_L1.9、[GPC3]H1_L1.10、[GPC3]H1_L1.16、[GPC3]H1_L1.23、[GPC3]H1_L1.29、[GPC3]H1_L1.31、[GPC3]H1_L1.65、[GPC3]H1_L1.66、[GPC3]H1_L1.67、[GPC3]H1_L1.68、[GPC3]H1_L1.70、[GPC3]H1_L1.71、[GPC3]H1_L1.72、[GPC3]H1_L1.73、[GPC3]H1.1_L1、[GPC3]H1.1_L1.1、[GPC3]H1.1_L1.2、[GPC3]H1.1_L1.3、[GPC3]H1.1_L1.4、[GPC3]H1.1_L1.5、[GPC3]H1.1_L1.6、[GPC3]H1.1_L1.7、[GPC3]H1.1_L1.8、[GPC3]H1.1_L1.9、[GPC3]H1.1_L1.10、[GPC3]H1.1_L1.16、[GPC3]H1.1_L1.23、[GPC3]H1.1_L1.29、[GPC3]H1.1_L1.31、[GPC3]H1.1_L1.65、[GPC3]H1.1_L1.66、L1.67、[GPC3]H1.1_L1.68、[GPC3]H1.1_L1.70、[GPC3]H1.1_L1.71、[GPC3]H1.1_L1.72、[GPC3]H1.1_L1.73、[GPC3]H1.2_L1、[GPC3]H1.2_L1.1、[GPC3]H1.2_L1.2、[GPC3]H1.2_L1.3、[GPC3]H1.2_L1.4、[GPC3]H1.2_L1.5、[GPC3]H1.2_L1.6、[GPC3]H1.2_L1.7、[GPC3]H1.2_L1.8、[GPC3]H1.2_L1.9、[GPC3]H1.2_L1.10、[GPC3]H1.2_L1.16、[GPC3]H1.2_L1.23、[GPC3]H1.2_L1.29、[GPC3]H1.2_L1.31、[GPC3]H1.2_L1.65、[GPC3]H1.2_L1.66、[GPC3]H1.2_L1.67、[GPC3]H1.2_L1.68、[GPC3]H1.2_L1.70、[GPC3]H1.2_L1.71、[GPC3]H1.2_L1.72、[GPC3]H1.2_L1.73、[GPC3]H1.3_L1、[GPC3]H1.3_L1.1、[GPC3]H1.3_L1.2、[GPC3]H1.3_L1.3、[GPC3]H1.3_L1.4、[GPC3]H1.3_L1.5、[GPC3]H1.3_L1.6、[GPC3]H1.3_L1.7、[GPC3]H1.3_L1.8、[GPC3]H1.3_L1.9、[GPC3]H1.3_L1.10、[GPC3]H1.3_L1.16、[GPC3]H1.3_L1.23、[GPC3]H1.3_L1.29、[GPC3]H1.3_L1.31、[GPC3]H1.3_L1.65、[GPC3]H1.3_L1.66、[GPC3]H1.3_L1.67、[GPC3]H1.3_L1.68、[GPC3]H1.3_L1.70、[GPC3]H1.3_L1.71、[GPC3]H1.3_L1.72、[GPC3]H1.3_L1.73、[GPC3]H1.4_L1、[GPC3]H1.4_L1.1、[GPC3]H1.4_L1.2、[GPC3]H1.4_L1.3、[GPC3]H1.4_L1.4、[GPC3]H1.4_L1.5、[GPC3]H1.4_L1.6、[GPC3]H1.4_L1.7、[GPC3]H1.4_L1.8、[GPC3]H1.4_L1.9、[GPC3]H1.4_L1.10、[GPC3]H1.4_L1.16、[GPC3]H1.4_L1.23、[GPC3]H1.4_L1.29、[GPC3]H1.4_L1.31、[GPC3]H1.4_L1.65、[GPC3]H1.4_L1.66、[GPC3]H1.4_L1.67、[GPC3]H1.4_L1.68、[GPC3]H1.4_L1.70、[GPC3]H1.4_L1.71、[GPC3]H1.4_L1.72和[GPC3]H1.4_L1.73或它们的变体。
在特定实施方案中，VH/VL对选自由[GPC3]H1.1_L1.16和[GPC3]H1.1_L1.69或它们的变体组成的组。
在一些实施方案中，1+1 Fab-scFv-Fc形式包含偏斜变体、pI变体、消融变体和FcRn变体。因此，一些实施方案包括1+1 Fab-scFv-Fc形式，其包含：a)第一单体(“scFv单体”)，该第一单体包含带电荷的scFv接头(在一些实施方案中，图5的+H序列是优选的)、偏斜变体S364K/E357Q、消融变体E233P/L234V/L235A/G236del/S267K、FcRn变体M428L/N434S和与如本文概述的CD3结合的scFv；b)第二单体(“Fab单体”)，该第二单体包含偏斜变体L368D/K370S、pI变体N208D/Q295E/N384D/Q418E/N421D、消融变体E233P/L234V/L235A/G236del/S267K、FcRn变体M428L/N434S和可变重链结构域；和c)轻链，该轻链包含可变轻链结构域(VL)和恒定轻链结构域(CL)，其中编号是根据EU编号进行的。可变重链结构域和可变轻链结构域构成GPC3结合结构域。尤其用于这些实施方案中的CD3结合结构域序列包括但不限于H1.30_L1.47、H1.32_L1.47、H1.89_L1.47、H1.90_L1.47、H1.33_L1.47、H1.31_L1.47、L1.47_H1.30、L1.47_H1.30、L1.47_H1.32、L1.47_H1.89、L1.47_H1.90、L1.47_H1.33和L1.47_H1.31或它们的变体，以及如图10中描绘的那些。在这些实施方案中特别有用的GPC3结合结构域序列包括但不限于选自由[GPC3]H1.1_L1.16和[GPC3]H1.1_L1.69组成的组的αGPC3 ABD VH/VL对。
用于与1+1形式抗体一起使用的特别有用的GPC3和CD3序列组合包括，例如，在图16和图17中公开。
图7A至图7D示出了在1+1 Fab-scFv-Fc形式抗体中有用的一些例示性Fc结构域序列。图7A至图7D中描绘的“单体1”序列通常是指“Fab-Fc重链”的Fc结构域，而“单体2”序列是指“scFv-Fc重链”的Fc结构域。此外，图9提供了可以此形式使用的有用CL序列。
在一些实施方案中，本文所描绘的任何VH和VL序列(包含附图和序列表中所描绘的所有VH和VL序列，包含针对GPC3的序列)可以使用附图和序列表中所示的任何抗CD3scFv序列添加到图7A至图7D的开瓶器主链形式作为“Fab侧”。
对于来自图7A的开瓶器主链1(任选地包含428L/434S变体)，尤其用于这些实施方案中的CD结合结构域序列包含但不限于CD3结合结构域抗CD3 H1.30_L1.47、抗CD3 H1.32_L1.47、抗CD3 H1.89_L1.47、抗CD3 H1.90_L1.47、抗CD3 H1.33_L1.47和抗CD3 H1.31_L1.47，其作为图7中所示的主链的scFv侧连接。
2.mAb-Fv
尤其用于本文所述的抗体中的一种异二聚支架是mAb-Fv形式(图44G)。在此实施方案中，该形式依赖于使用“额外”可变重链结构域与一个单体的C末端附接，以及“额外”可变轻链结构域与另一单体的C末端连接，因此形成第三抗原结合结构域，其中两种单体的Fab部分结合GPC3且“额外”scFv结构域结合CD3。
在这个实施方案中，第一单体包含第一重链，其包含第一可变重链结构域和包括第一Fc结构域的第一重链恒定结构域，其中第一可变轻链结构域使用结构域接头共价附接到第一Fc结构域的C末端(VH1-CH1-铰链-CH2-CH3-[任选的接头]-VL2)。第二单体包含第二可变重链结构域，其属于包括第二Fc结构域的第二重链恒定结构域，和第三可变重链结构域，其使用结构域接头共价连接到第二Fc结构域的C末端(vh1-CH1-铰链-CH2-CH3-[任选的接头]-VH2)。两个C末端附接的可变结构域构成与CD3结合的Fv(因为具有二价CD3结合是较不优选的)。这个实施方案进一步利用包含可变轻链结构域和恒定轻链结构域的共同轻链，该共同轻链与重链缔合而形成结合GPC3的两个相同Fab。就本文的许多实施方案来说，这些构建体包含如所期望并且本文所述的偏斜变体、pI变体、消融变体、另外的Fc变体等。
本文所述的抗体提供mAb-Fv形式或它们的变体，其中CD3结合结构域序列如图10所示。本文所述的抗体提供mAb-Fv形式或它们的变体，其中GPC3结合结构域序列如图12和图13所示。
另外，mAb-Fv形式的Fc结构域包含偏斜变体(例如，如图1所示的一组氨基酸取代，其中特别有用的偏斜变体选自由以下组成的组：S364K/E357Q:L368D/K370S；L368D/K370S:S364K；L368E/K370S:S364K；T411T/E360E/Q362E:D401K；L368D/K370S:S364K/E357L、K370S:S364K/E357Q、T366S/L368A/Y407V:T366W和T366S/L368A/Y407V/Y349C:T366W/S354C)、任选的消融变体(包括图3中示出的那些)、任选的带电荷的scFv接头(包括图5中示出的那些)，并且重链包含pI变体(包括图2中示出的那些)。
在一些实施方案中，mAb-Fv形式包含偏斜变体、pI变体和消融变体。因此，一些实施方案包括mAb-Fv形式，其包含：a)第一单体，该第一单体包含偏斜变体S364K/E357Q、消融变体E233P/L234V/L235A/G236del/S267K以及与轻链的第一可变轻链结构域一起构成与GPC3结合的Fv的第一可变重链结构域，和第二可变重链结构域；b)第二单体，该第二单体包含偏斜变体L368D/K370S、pI变体N208D/Q295E/N384D/Q418E/N421D、消融变体E233P/L234V/L235A/G236del/S267K，和与第一可变轻链结构域一起构成与如本文概述的GPC3结合的Fv的第一可变重链结构域，以及与第二可变重链结构域一起形成与CD3结合的Fv(ABD)的第二可变轻链；和c)轻链，该轻链包含第一可变轻链结构域和恒定轻链结构域。
在一些实施方案中，mAb-Fv形式包含偏斜变体、pI变体、消融变体和FcRn变体。因此，一些实施方案包括mAb-Fv形式，其包含：a)第一单体，该第一单体包含偏斜变体S364K/E357Q、消融变体E233P/L234V/L235A/G236del/S267K、FcRn变体M428L/N434S以及与轻链的第一可变轻链结构域一起构成与GPC3结合的Fv的第一可变重链结构域，和第二可变重链结构域；b)第二单体，该第二单体包含偏斜变体L368D/K370S、pI变体N208D/Q295E/N384D/Q418E/N421D、消融变体E233P/L234V/L235A/G236del/S267K、FcRn变体M428L/N434S，和与第一可变轻链结构域一起构成与如本文概述的GPC3结合的Fv的第一可变重链结构域，以及与第一单体的第二可变重链结构域一起形成结合CD3的Fv(ABD)的第二可变轻链；和c)轻链，该轻链包含第一可变轻链结构域和恒定轻链结构域。
3.mAb-scFv
尤其用于本文所述的抗体中的一种异二聚支架是mAb-scFv形式(图44H)。在此实施方案中，该形式依赖于使用scFv与单体之一的C末端附接，从而形成第三抗原结合结构域，其中两个单体的Fab部分结合GPC3并且“额外”scFv结构域结合CD3。因此，第一单体包含第一重链(包含可变重链结构域和恒定结构域)，且C末端共价连接scFv，其包括scFv可变轻链结构域、scFv接头以及scFv可变重链结构域，呈任一取向(VH1-CH1-铰链-CH2-CH3-[任选的接头]-VH2-scFv接头-VL2或VH1-CH1-铰链-CH2-CH3-[任选的接头]-VL2-scFv接头-VH2)。这个实施方案进一步利用包含可变轻链结构域和恒定轻链结构域的共同轻链，所述共同轻链与重链缔合而形成结合GPC3的两个相同Fab。就本文的许多实施方案来说，这些构建体包含如所期望并且本文所述的偏斜变体、pI变体、消融变体、另外的Fc变体等。
本文所述的抗体提供mAb-scFv形式或它们的变体，其中CD结合结构域序列如图10A至图10F所示，并且GPC3结合结构域序列或它们的变体如图12和图13所示。
另外，mAb-scFv形式的Fc结构域包含偏斜变体(例如，如图1所示的一组氨基酸取代，其中特别有用的偏斜变体选自由以下组成的组：S364K/E357Q:L368D/K370S；L368D/K370S:S364K；L368E/K370S:S364K；T411T/E360E/Q362E:D401K；L368D/K370S:S364K/E357L、K370S:S364K/E357Q、T366S/L368A/Y407V:T366W和T366S/L368A/Y407V/Y349C:T366W/S354C)、任选的消融变体(包括图3中示出的那些)、任选的带电荷的scFv接头(包括图5中示出的那些)，并且重链包含pI变体(包括图2中示出的那些)。
在一些实施方案中，mAb-scFv形式包含偏斜变体、pI变体和消融变体。因此，一些实施方案包括mAb-Fv形式，其包含：a)第一单体，该第一单体包含偏斜变体S364K/E357Q、消融变体E233P/L234V/L235A/G236del/S267K以及与共同轻链的可变轻链结构域一起构成与如本文概述的GPC3结合的Fv的可变重链结构域，和与CD3结合的scFv结构域；b)第二单体，该第二单体包含偏斜变体L368D/K370S、pI变体N208D/Q295E/N384D/Q418E/N421D、消融变体E233P/L234V/L235A/G236del/S267K以及与共同轻链的可变轻链结构域一起构成与如本文概述的GPC3结合的Fv的可变重链结构域；和c)共同轻链，该共同轻链包含可变轻链结构域和恒定轻链结构域。
在一些实施方案中，mAb-scFv形式包含偏斜变体、pI变体、消融变体和FcRn变体。因此，一些实施方案包括mAb-Fv形式，其包含：a)第一单体，该第一单体包含偏斜变体S364K/E357Q、消融变体E233P/L234V/L235A/G236del/S267K、FcRn变体M428L/N434S以及与共同轻链的可变轻链结构域一起构成与如本文概述的GPC3结合的Fv的可变重链结构域，和与CD3结合的scFv结构域；b)第二单体，该第二单体包含偏斜变体L368D/K370S、pI变体N208D/Q295E/N384D/Q418E/N421D、消融变体E233P/L234V/L235A/G236del/S267K、FcRn变体M428L/N434S以及与共同轻链的可变轻链结构域一起构成与如本文概述的GPC3结合的Fv的可变重链结构域；和c)共同轻链，该共同轻链包含可变轻链结构域和恒定轻链结构域。
4. 2+1 Fab2-scFv-Fc形式
发现尤其用于本文所述的抗体中的一种异二聚支架是“2+1 Fab2-scFv-Fc”形式(在之前的相关文件中也被称为“中心-scFv形式”)，如图15B所示，具有CD3结合结构域和两个肿瘤靶抗原(GPC3)结合结构域的示例性组合。在此实施方案中，该形式依赖于插入的scFv结构域的使用，从而形成第三抗原结合结构域，其中两个单体的Fab部分结合GPC3，并且“额外”scFv结构域结合CD3。将scFv结构域插入一种单体的Fc结构域与CH1-Fv区之间，从而提供第三抗原结合结构域。例如，具有2+1 Fab2-scFv-Fc形式的GPC3×CD3双特异性抗体在表达低水平的GPC3的细胞环境中在诱导重定向T细胞细胞毒性方面是有效的。此外，如示例中所示，具有2+1 Fab2-scFv-Fc形式的GPC3×CD3双特异性抗体允许免疫应答的“微调”，因为此类抗体表现出各种各样的不同性质，这取决于所使用的GPC3和/或CD3结合结构域。例如，此类抗体在对具有不同GPC3表达的细胞的选择性、对于GPC3表达性细胞的效力、引发细胞因子释放的能力以及对可溶性GPC3的敏感性方面表现出差异。这些GPC3抗体可用于例如治疗GPC3相关癌症。
在此实施方案中，一个单体包括第一重链，该第一重链包括第一可变重链结构域、CH1结构域(以及任选的铰链)和Fc结构域，其中scFv包括scFv可变轻链结构域、scFv接头和scFv可变重链结构域。scFv使用任选的结构域接头共价连接在重链恒定结构域的CH1结构域的C末端与第一Fc结构域的N末端之间(VH1-CH1-[任选的接头]-VH2-scFv接头-VL2-[包括铰链的任选的接头]-CH2-CH3，或scFv的相反取向VH1-CH1-[任选的接头]-VL2-scFv接头-VH2-[包括铰链的任选的接头]-CH2-CH3)。任选的接头可以是任何合适的肽接头，包括例如图6中包括的结构域接头。在一些实施方案中，任选的接头是铰链或其片段。另一个单体是标准Fab侧(即，VH1-CH1-铰链-CH2-CH3)。这个实施方案进一步利用包含可变轻链结构域和恒定轻链结构域的共同轻链，该共同轻链与重链缔合而形成结合GPC3的两个相同Fab。就本文的许多实施方案来说，这些构建体包含如所期望并且本文所述的偏斜变体、pI变体、消融变体、另外的Fc变体等。
在一个实施方案中，2+1 Fab2-scFv-Fc形式抗体包含具有图10中所描绘的CD3结合结构域序列的VH和VL的scFv。在一个实施方案中，2+1Fab2-scFv-Fc形式抗体包含具有如图12和图13中所示的GPC3结合结构域的VH和VL的两个Fab。
在示例性实施方案中，2+1 Fab2-scFv-Fc GPC3×CD3双特异性抗体的GPC3结合结构域包括VH和VL。尤其用于这些实施方案中的CD3结合结构域序列包括但不限于H1.30_L1.47、H1.32_L1.47、H1.89_L1.47、H1.90_L1.47、H1.33_L1.47、H1.31_L1.47、L1.47_H1.30、L1.47_H1.30、L1.47_H1.32、L1.47_H1.89、L1.47_H1.90、L1.47_H1.33和L1.47_H1.31或它们的变体，以及在WO2014/145806的图10中描绘的那些以及图14和图15中描绘的那些，所述文献特此通过引用并入(包括图例)。
任何合适的GPC3 ABD可包含在2+1 Fab2-scFv-Fc形式抗体中，包括本文提供的那些。在这些实施方案中特别有用的GPC3 ABD包括但不限于选自由以下组成的组的VH和VL结构域：[GPC3]H1_L1、[GPC3]H1_L1.1、[GPC3]H1_L1.2、[GPC3]H1_L1.3、[GPC3]H1_L1.4、[GPC3]H1_L1.5、[GPC3]H1_L1.6、[GPC3]H1_L1.7、[GPC3]H1_L1.8、[GPC3]H1_L1.9、[GPC3]H1_L1.10、[GPC3]H1_L1.16、[GPC3]H1_L1.23、[GPC3]H1_L1.29、[GPC3]H1_L1.31、[GPC3]H1_L1.65、[GPC3]H1_L1.66、[GPC3]H1_L1.67、[GPC3]H1_L1.68、[GPC3]H1_L1.70、[GPC3]H1_L1.71、[GPC3]H1_L1.72、[GPC3]H1_L1.73、[GPC3]H1.1_L1、[GPC3]H1.1_L1.1、[GPC3]H1.1_L1.2、[GPC3]H1.1_L1.3、[GPC3]H1.1_L1.4、[GPC3]H1.1_L1.5、[GPC3]H1.1_L1.6、[GPC3]H1.1_L1.7、[GPC3]H1.1_L1.8、[GPC3]H1.1_L1.9、[GPC3]H1.1_L1.10、[GPC3]H1.1_L1.16、[GPC3]H1.1_L1.23、[GPC3]H1.1_L1.29、[GPC3]H1.1_L1.31、[GPC3]H1.1_L1.65、[GPC3]H1.1_L1.66、L1.67、[GPC3]H1.1_L1.68、[GPC3]H1.1_L1.70、[GPC3]H1.1_L1.71、[GPC3]H1.1_L1.72、[GPC3]H1.1_L1.73、[GPC3]H1.2_L1、[GPC3]H1.2_L1.1、[GPC3]H1.2_L1.2、[GPC3]H1.2_L1.3、[GPC3]H1.2_L1.4、[GPC3]H1.2_L1.5、[GPC3]H1.2_L1.6、[GPC3]H1.2_L1.7、[GPC3]H1.2_L1.8、[GPC3]H1.2_L1.9、[GPC3]H1.2_L1.10、[GPC3]H1.2_L1.16、[GPC3]H1.2_L1.23、[GPC3]H1.2_L1.29、[GPC3]H1.2_L1.31、[GPC3]H1.2_L1.65、[GPC3]H1.2_L1.66、[GPC3]H1.2_L1.67、[GPC3]H1.2_L1.68、[GPC3]H1.2_L1.70、[GPC3]H1.2_L1.71、[GPC3]H1.2_L1.72、[GPC3]H1.2_L1.73、[GPC3]H1.3_L1、[GPC3]H1.3_L1.1、[GPC3]H1.3_L1.2、[GPC3]H1.3_L1.3、[GPC3]H1.3_L1.4、[GPC3]H1.3_L1.5、[GPC3]H1.3_L1.6、[GPC3]H1.3_L1.7、[GPC3]H1.3_L1.8、[GPC3]H1.3_L1.9、[GPC3]H1.3_L1.10、[GPC3]H1.3_L1.16、[GPC3]H1.3_L1.23、[GPC3]H1.3_L1.29、[GPC3]H1.3_L1.31、[GPC3]H1.3_L1.65、[GPC3]H1.3_L1.66、[GPC3]H1.3_L1.67、[GPC3]H1.3_L1.68、[GPC3]H1.3_L1.70、[GPC3]H1.3_L1.71、[GPC3]H1.3_L1.72、[GPC3]H1.3_L1.73、[GPC3]H1.4_L1、[GPC3]H1.4_L1.1、[GPC3]H1.4_L1.2、[GPC3]H1.4_L1.3、[GPC3]H1.4_L1.4、[GPC3]H1.4_L1.5、[GPC3]H1.4_L1.6、[GPC3]H1.4_L1.7、[GPC3]H1.4_L1.8、[GPC3]H1.4_L1.9、[GPC3]H1.4_L1.10、[GPC3]H1.4_L1.16、[GPC3]H1.4_L1.23、[GPC3]H1.4_L1.29、[GPC3]H1.4_L1.31、[GPC3]H1.4_L1.65、[GPC3]H1.4_L1.66、[GPC3]H1.4_L1.67、[GPC3]H1.4_L1.68、[GPC3]H1.4_L1.70、[GPC3]H1.4_L1.71、[GPC3]H1.4_L1.72和[GPC3]H1.4_L1.73或它们的变体。
在特定实施方案中，VH/VL对选自由[GPC3]H1.1_L1.16和[GPC3]H1.1_L1.69或它们的变体组成的组。
另外，2+1 Fab2-scFv-Fc形式的Fc结构域包含偏斜变体(例如，如图1所示的一组氨基酸取代，其中特别有用的偏斜变体选自由以下组成的组：S364K/E357Q:L368D/K370S；L368D/K370S:S364K；L368E/K370S:S364K；T411T/E360E/Q362E:D401K；L368D/K370S:S364K/E357L、K370S:S364K/E357Q、T366S/L368A/Y407V:T366W和T366S/L368A/Y407V/Y349C:T366W/S354C)、任选的消融变体(包括图3中示出的那些)、任选的带电荷的scFv接头(包括图5中示出的那些)，并且重链包含pI变体(包括图2中示出的那些)。
在一些实施方案中，2+1 Fab2-scFv-Fc形式抗体包含偏斜变体、pI变体和消融变体。因此，一些实施方案包括2+1 Fab2-scFv-Fc形式，其包含：a)第一单体(Fab-scFv-Fc侧)，该第一单体包含偏斜变体S364K/E357Q、消融变体E233P/L234V/L235A/G236del/S267K以及与共同轻链的可变轻链结构域一起构成与如本文概述的GPC3结合的Fv的可变重链结构域，和与CD3结合的scFv结构域；b)第二单体(Fab-Fc侧)，该第二单体包含偏斜变体L368D/K370S、pI变体N208D/Q295E/N384D/Q418E/N421D、消融变体E233P/L234V/L235A/G236del/S267K以及与共同轻链的可变轻链结构域一起构成与如本文概述的GPC3结合的Fv的可变重链结构域；和c)共同轻链，该共同轻链包含可变轻链结构域和恒定轻链结构域，其中编号是根据EU编号进行的。在一些实施方案中，αGPC3 VH/VL对选自由[GPC3]H1.1_L1.16和[GPC3]H1.1_L1.69组成的组。
在一些实施方案中，2+1 Fab2-scFv-Fc形式抗体包含偏斜变体、pI变体、消融变体和FcRn变体。因此，一些实施方案包括2+1 Fab2-scFv-Fc形式，其包含：a)第一单体(Fab-scFv-Fc侧)，该第一单体包含偏斜变体S364K/E357Q、消融变体E233P/L234V/L235A/G236del/S267K、FcRn变体M428L/N434S以及与共同轻链的可变轻链结构域一起构成与如本文概述的GPC3结合的Fv的可变重链结构域，和与CD3结合的scFv结构域；b)第二单体(Fab-Fc侧)，该第二单体包含偏斜变体L368D/K370S、pI变体N208D/Q295E/N384D/Q418E/N421D、消融变体E233P/L234V/L235A/G236del/S267K、FcRn变体M428L/N434S以及与共同轻链的可变轻链结构域一起构成与如本文概述的GPC3结合的Fv的可变重链结构域；和c)共同轻链，该共同轻链包含可变轻链结构域和恒定轻链结构域，其中编号是根据EU编号进行的。在一些实施方案中，αGPC3 VH/VL对选自由[GPC3]H1.1_L1.16和[GPC3]H1.1_L1.69组成的组。尤其用于这些实施方案中的CD3结合结构域序列包括但不限于H1.30_L1.47、H1.32_L1.47、H1.89_L1.47、H1.90_L1.47、H1.33_L1.47、H1.31_L1.47、L1.47_H1.30、L1.47_H1.30、L1.47_H1.32、L1.47_H1.89、L1.47_H1.90、L1.47_H1.33和L1.47_H1.31或它们的变体。
图8A至图8C示出了一些示例性Fc结构域序列，该Fc结构域序列可用于2+1 Fab2-scFv-Fc形式。图8A至图8C中描绘的“单体1”序列通常是指“Fab-Fc重链”的Fc结构域，而“单体2”序列是指“Fab-scFv-Fc重链”的Fc结构域。此外，图9提供了可以此形式使用的有用CL序列。
图18至图21中描绘了示例性抗GPC3×抗CD3 2+1 Fab2-scFv-Fc形式抗体。
5.中心Fv
尤其用于本文所述的抗体中的一种异二聚支架是中心-Fv形式(图44I)。在此实施方案中，该形式依赖于使用插入的Fv结构域(即，中心Fv结构域)，从而形成“额外”第三抗原结合结构域，其中两个单体的Fab部分结合GPC3并且“额外”中心Fv结构域结合CD3。“额外”中心Fv结构域被插入在Fc结构域与单体的CH1-Fv区之间，从而提供第三抗原结合结构域(即，“额外”中心Fv结构域)，其中每个单体含有“额外”中心Fv结构域的组分(即，一个单体包括可变重链结构域，并且另一个包括“额外”中心Fv结构域的可变轻链结构域)。
在这个实施方案中，一个单体包含第一重链，该第一重链包含第一可变重链结构域、CH1结构域以及Fc结构域和另外的可变轻链结构域。该轻链结构域使用结构域接头共价连接在重链恒定结构域的CH1结构域的C末端与第一Fc结构域的N末端之间(VH1-CH1-[任选的接头]-VL2-铰链-CH2-CH3)。另一个单体包括第一重链，所述第一重链包括第一可变重链结构域、CH1结构域和Fc结构域以及另外的可变重链结构域(VH1-CH1-[任选的接头]-VH2-铰链-CH2-CH3)。该轻链结构域使用结构域接头共价连接在重链恒定结构域的CH1结构域的C末端与第一Fc结构域的N末端之间。
这个实施方案进一步利用包含可变轻链结构域和恒定轻链结构域的共同轻链，该述共同轻链与重链缔合而形成各自结合GPC3的两个相同Fab。就本文的许多实施方案来说，这些构建体包含如所期望并且本文所述的偏斜变体、pI变体、消融变体、另外的Fc变体等。
本文所述的抗体提供中心-Fv形式或它们的变体，其中CD3结合结构域序列如图10所示，并且GPC3结合结构域序列或它们的变体如图12和图13所示。
6.单臂中心-scFv
尤其用于本文所述的抗体中的一种异二聚支架是单臂中心-scFv形式(图44C)。在此实施方案中，一种单体仅包括Fc结构域，而另一种单体包含Fab结构域(第一抗原结合结构域)、scFv结构域(第二抗原结合结构域)和Fc结构域，其中scFv结构域被插入在Fc结构域与Fc结构域之间。在此形式下，Fab部分与一个受体靶标结合，并且scFv与另一个受体靶标结合。在此形式下，Fab部分结合GPC3并且scFv结合CD3，或反之亦然。
在此实施方案中，一个单体包括第一重链，该第一重链包括第一可变重链结构域、CH1结构域和Fc结构域，其中scFv包括scFv可变轻链结构域、scFv接头和scFv可变重链结构域。scFv使用结构域接头在任一朝向上共价连接在重链恒定结构域的CH1结构域的C末端与第一Fc结构域的N末端之间(VH1-CH1-[任选的结构域接头]-VH2-scFv接头-VL2-[任选的结构域接头]-CH2-CH3或VH1-CH1-[任选的结构域接头]-VL2-scFv接头-VH2-[任选的结构域接头]-CH2-CH3)。第二单体包含Fc结构域(CH2-CH3)。此实施方案进一步利用了包括可变轻链结构域和恒定轻链结构域的轻链，该轻链与重链缔合以形成Fab。
就本文的许多实施方案来说，这些构建体包含如所期望并且本文所述的偏斜变体、pI变体、消融变体、另外的Fc变体等。
本文所述的抗体提供中心-Fv形式或它们的变体，其中CD3结合结构域序列如图10所示，并且GPC3结合结构域序列或它们的变体如图12和图13所示。
另外，单臂中心-scFv形式的Fc结构域通常包括偏斜变体(例如，如图1所示的一组氨基酸取代，其中特别有用的偏斜变体选自由以下组成的组：S364K/E357Q:L368D/K370S；L368D/K370S:S364K；L368E/K370S:S364K；T411T/E360E/Q362E:D401K；L368D/K370S:S364K/E357L、K370S:S364K/E357Q、T366S/L368A/Y407V:T366W和T366S/L368A/Y407V/Y349C:T366W/S354C)、任选的消融变体(包括图3中示出的那些)、任选的带电荷的scFv接头(包括图5中示出的那些)，并且重链包含pI变体(包括图2中示出的那些)。
在一些实施方案中，单臂中心-scFv形式包含偏斜变体、pI变体和消融变体。因此，单臂中心-scFv形式的一些实施方案包含：a)第一单体，该第一单体包含偏斜变体S364K/E357Q、消融变体E233P/L234V/L235A/G236del/S267K以及与轻链的可变轻链结构域一起构成与如本文概述的GPC3结合的Fv的可变重链结构域，和与CD3结合的scFv结构域；b)第二单体，该第二单体包含具有偏斜变体L368D/K370S、pI变体N208D/Q295E/N384D/Q418E/N421D、消融变体E233P/L234V/L235A/G236del/S267K的Fc结构域；和c)轻链，该轻链包含可变轻链结构域和恒定轻链结构域。
在一些实施方案中，单臂中心-scFv形式包含偏斜变体、pI变体、消融变体和FcRn变体。因此，单臂中心-scFv形式的一些实施方案包含：a)第一单体，该第一单体包含偏斜变体S364K/E357Q、消融变体E233P/L234V/L235A/G236del/S267K、FcRn变体M428L/N434S以及与轻链的可变轻链结构域一起构成与如本文概述的GPC3结合的Fv的可变重链结构域，和与CD3结合的scFv结构域；b)第二单体，该第二单体包含具有偏斜变体L368D/K370S、pI变体N208D/Q295E/N384D/Q418E/N421D、消融变体E233P/L234V/L235A/G236del/S267K和FcRn变体M428L/N434S的Fc结构域；和c)轻链，该轻链包含可变轻链结构域和恒定轻链结构域。
7.单臂scFv-mAb
尤其用于本文所述的抗体中的一种异二聚支架是单臂scFv-mAb形式(图44D)。在这个实施方案中，一个单体仅包含Fc结构域，而另一个单体使用连接到重链的N末端的scFv结构域，通常通过使用接头：VH-scFv接头-VL-[任选的结构域接头]-CH1-铰链-CH2-CH3或(呈相反取向)VL-scFv接头-VH-[任选的结构域接头]-CH1-铰链-CH2-CH3。以此形式，Fab部分各自结合GPC3并且scFv结合CD3。这个实施方案进一步利用包含可变轻链结构域和恒定轻链结构域的轻链，该轻链与重链缔合而形成Fab。就本文的许多实施方案来说，这些构建体包含如所期望并且本文所述的偏斜变体、pI变体、消融变体、另外的Fc变体等。
本文所述的抗体提供单臂scFv-mAb形式或它们的变体，其中CD3结合结构域序列如图10所示，并且其中GPC3结合结构域序列或它们的变体如图12和图13所示。
另外，单臂scFv-mAb形式的Fc结构域通常包括偏斜变体(例如，如图1所示的一组氨基酸取代，其中特别有用的偏斜变体选自由以下组成的组：S364K/E357Q:L368D/K370S；L368D/K370S:S364K；L368E/K370S:S364K；T411T/E360E/Q362E:D401K；L368D/K370S:S364K/E357L、K370S:S364K/E357Q、T366S/L368A/Y407V:T366W和T366S/L368A/Y407V/Y349C:T366W/S354C)、任选的消融变体(包括图3中示出的那些)、任选的带电荷的scFv接头(包括图5中示出的那些)，并且重链包含pI变体(包括图2中示出的那些)。
在一些实施方案中，单臂scFv-mAb形式包含偏斜变体、pI变体和消融变体。因此，单臂scFv-mAb形式的一些实施方案包含：a)第一单体，该第一单体包含偏斜变体S364K/E357Q、消融变体E233P/L234V/L235A/G236del/S267K以及与轻链的可变轻链结构域一起构成与如本文概述的GPC3结合的Fv的可变重链结构域，和与CD3结合的scFv结构域；b)第二单体，该第二单体包含具有偏斜变体L368D/K370S、pI变体N208D/Q295E/N384D/Q418E/N421D、消融变体E233P/L234V/L235A/G236del/S267K的Fc结构域；和c)轻链，该轻链包含可变轻链结构域和恒定轻链结构域。
在一些实施方案中，单臂scFv-mAb形式包含偏斜变体、pI变体、消融变体和FcRn变体。因此，一些实施方案单臂scFv-mAb形式包含：a)第一单体，该第一单体包含偏斜变体S364K/E357Q、消融变体E233P/L234V/L235A/G236del/S267K、FcRn变体M428L/N434S以及与轻链的可变轻链结构域一起构成与如本文概述的GPC3结合的Fv的可变重链结构域，和与CD3结合的scFv结构域；b)第二单体，该第二单体包含具有偏斜变体L368D/K370S、pI变体N208D/Q295E/N384D/Q418E/N421D、消融变体E233P/L234V/L235A/G236del/S267K和FcRn变体M428L/N434S的Fc结构域；和c)轻链，该轻链包含可变轻链结构域和恒定轻链结构域。
8.scFv-mAb
尤其用于本文所述的抗体中的一种异二聚支架是mAb-scFv形式(图44E)。在此实施方案中，该形式依赖于使用scFv与单体之一的N末端附接，从而形成第三抗原结合结构域，其中两个单体的Fab部分结合GPC3并且“额外”scFv结构域结合CD3。
在此实施方案中，第一单体包括第一重链(包括可变重链结构域和恒定结构域)，其中N末端共价连接的scFv包括在任一朝向上的scFv可变轻结构域、scFv接头和scFv可变重链结构域((VH1-scFv接头-VL1-[任选的结构域接头]-VH2-CH1-铰链-CH2-CH3)或(scFv在相反朝向上)((VL1-scFv接头-VH1-[任选的结构域接头]-VH2-CH1-铰链-CH2-CH3))。这个实施方案进一步利用包含可变轻链结构域和恒定轻链结构域的共同轻链，该共同轻链与重链缔合而形成结合GPC3的两个相同Fab。就本文的许多实施方案来说，这些构建体包含如所期望并且本文所述的偏斜变体、pI变体、消融变体、另外的Fc变体等。
本文所述的抗体提供scFv-mAb形式或它们的变体，其中CD3结合结构域序列如图10所示，并且其中GPC3结合结构域序列或它们的变体如图12和图13所示。
另外，scFv-mAb形式的Fc结构域通常包括偏斜变体(例如，如图1所示的一组氨基酸取代，其中特别有用的偏斜变体选自由以下组成的组：S364K/E357Q:L368D/K370S；L368D/K370S:S364K；L368E/K370S:S364K；T411T/E360E/Q362E:D401K；L368D/K370S:S364K/E357L、K370S:S364K/E357Q、T366S/L368A/Y407V:T366W和T366S/L368A/Y407V/Y349C:T366W/S354C)、任选的消融变体(包括图3中示出的那些)、任选的带电荷的scFv接头(包括图5中示出的那些)，并且重链包含pI变体(包括图2中示出的那些)。
在一些实施方案中，scFv-mAb形式包含偏斜变体、pI变体和消融变体。因此，一些实施方案包括scFv-mAb形式，其包含：a)第一单体，该第一单体包含偏斜变体S364K/E357Q、消融变体E233P/L234V/L235A/G236del/S267K以及与共同轻链的可变轻链结构域一起构成与如本文概述的GPC3结合的Fv的可变重链结构域，和与CD3结合的scFv结构域；b)第二单体，该第二单体包含偏斜变体L368D/K370S、pI变体N208D/Q295E/N384D/Q418E/N421D、消融变体E233P/L234V/L235A/G236del/S267K以及与共同轻链的可变轻链结构域一起构成与如本文概述的GPC3结合的Fv的可变重链结构域；和c)共同轻链，该共同轻链包含可变轻链结构域和恒定轻链结构域。
在一些实施方案中，scFv-mAb形式包含偏斜变体、pI变体、消融变体和FcRn变体。因此，一些实施方案包括scFv-mAb形式，其包含：a)第一单体，该第一单体包含偏斜变体S364K/E357Q、消融变体E233P/L234V/L235A/G236del/S267K、FcRn变体M428L/N434S以及与共同轻链的可变轻链结构域一起构成与如本文概述的GPC3结合的Fv的可变重链结构域，和与CD3结合的scFv结构域；b)第二单体，该第二单体包含偏斜变体L368D/K370S、pI变体N208D/Q295E/N384D/Q418E/N421D、消融变体E233P/L234V/L235A/G236del/S267K、FcRn变体M428L/N434S以及与共同轻链的可变轻链结构域一起构成与如本文概述的GPC3结合的Fv的可变重链结构域；和c)共同轻链，该共同轻链包含可变轻链结构域和恒定轻链结构域。
9.双scFv形式
本文所述的抗体还提供了本领域已知的双scFv形式(图44B)。在这个实施方案中，GPC3×CD3异二聚双特异性抗体由两个scFv-Fc单体构成(两个单体皆呈(VH-scFv接头-VL-[任选的结构域接头]-CH2-CH3)形式或(VL-scFv接头-VH-[任选的结构域接头]-CH2-CH3)形式，或一个单体一种取向且另一个单体另一种取向)。
本文所述的抗体提供双scFv形式或它们的变体，其中CD3结合结构域序列如图10所示，并且其中GPC3结合结构域序列或它们的变体如图12和图13所示。
在一些实施方案中，双scFv形式包含偏斜变体、pI变体和消融变体。因此，一些实施方案包括双scFv形式，其包含：a)第一单体，该第一单体包含偏斜变体S364K/E357Q、消融变体E233P/L234V/L235A/G236del/S267K以及结合CD3或GPC3的第一scFv；和b)第二单体，该第二单体包含偏斜变体L368D/K370S、pI变体N208D/Q295E/N384D/Q418E/N421D、消融变体E233P/L234V/L235A/G236del/S267K以及结合CD3或GPC3的第二scFv。在一些实施方案中，双scFv形式包含偏斜变体、pI变体、消融变体和FcRn变体。在一些实施方案中，双scFv形式包含偏斜变体、pI变体和消融变体。因此，一些实施方案包括双scFv形式，其包含：a)第一单体，该第一单体包含偏斜变体S364K/E357Q、消融变体E233P/L234V/L235A/G236del/S267K、FcRn变体M428L/N434S以及结合CD3或GPC3的第一scFv；和b)第二单体，该第二单体包含偏斜变体L368D/K370S、pI变体N208D/Q295E/N384D/Q418E/N421D、消融变体E233P/L234V/L235A/G236del/S267K、FcRn变体M428L/N434S和结合CD3或GPC3的第二scFv。
10.非异二聚双特异性抗体
如本领域技术人员将理解的，本文提供的抗GPC3×抗CD3抗体也可以非异二聚双特异性形式包含在内(参见图44J)。以此形式，抗GPC3×抗CD3包括：1)包含VH1-CH1-铰链-CH2-CH3的第一单体；2)包含VH2-CH1-铰链-CH2-CH3的第二单体；3)包含VL1-CL的第一轻链；和4)包含VL2-CL的第二轻链。在此类实施方案中，VH1和VL1形成第一抗原结合结构域，并且VH2和VL2形成第二抗原结合结构域。第一抗原结合结构域或第二抗原结合结构域中的一者结合GPC3，并且另一抗原结合结构域结合CD3。
任何合适的GPC3结合结构域和CD3结合结构域可以非异二聚双特异性抗体形式包含在抗GPC3×抗CD3抗体中，包括本文提供的GPC3结合结构域和CD3结合结构域以及相关VH和VL或它们的变体中的任一者(参见例如图10、图12和图13)。
11.三叉形式
在一些实施方案中，本文所述的双特异性抗体呈如在WO2015/184203中总体上描述的“三叉”形式，所述文献特此通过引用整体明确并入，特别是针对“异源二聚体促进结构域”或“HPD”的附图、图例、定义和的序列(包含“K螺旋”和“E螺旋”序列)而明确并入。三叉依赖于使用两种不同的HPD，该两种不同的HPD缔合以形成异源二聚体结构作为结构的组分。在此实施方案中，三叉形式包含“传统的”重链和轻链(例如，VH1-CH1-铰链-CH2-CH3和VL1-CL)、包括第一“双抗体型结合结构域”或VH2-(接头)-VL3-HPD1的第三链以及包括第二、VH3-(接头)-(接头)-VL2-HPD2的第四链。VH1和VL1形成第一ABD，VH2和VL2形成第二ABD，并且VH3和VL3形成第三ABD。在一些情况下，如图1K中所示，第二ABD和第三ABD结合同一抗原，在这种情况下通常是GPC3，例如二价地，其中第一ABD单价地结合CD3。
任何合适的GPC3结合结构域和CD3结合结构域可以三叉双特异性抗体形式包含在抗GPC3×抗CD3抗体中，包括本文提供的GPC3结合结构域和CD3结合结构域以及相关VH和VL或它们的变体中的任一者(参见例如图10、图12和图13)。
12.单特异性的单克隆抗体
如本领域的技术人员将理解的，本文概述的新型Fv序列还可以用于单特异性抗体(例如，“传统单克隆抗体”)或非异二聚双特异性形式两者。因此，在一些实施方案中，本文所述的抗体提供了单克隆(单特异性)抗体，所述单克隆抗体包括6个CDR和/或来自附图的vh和vl序列，通常具有IgG1、IgG2、IgG3或IgG4恒定区，其中IgG1、IgG2和IgG4(包含包括S228P氨基酸取代的IgG4恒定区)特别用于一些实施方案。也就是说，本文中的具有“H_L”名称的任何序列可以连接到人IgG1抗体的恒定区。
在一些实施方案中，单特异性抗体是具有选自由以下组成的组的VH/VL对的GPC3单特异性抗体：[GPC3]H1_L1、[GPC3]H1_L1.1、[GPC3]H1_L1.2、[GPC3]H1_L1.3、[GPC3]H1_L1.4、[GPC3]H1_L1.5、[GPC3]H1_L1.6、[GPC3]H1_L1.7、[GPC3]H1_L1.8、[GPC3]H1_L1.9、[GPC3]H1_L1.10、[GPC3]H1_L1.16、[GPC3]H1_L1.23、[GPC3]H1_L1.29、[GPC3]H1_L1.31、[GPC3]H1_L1.65、[GPC3]H1_L1.66、[GPC3]H1_L1.67、[GPC3]H1_L1.68、[GPC3]H1_L1.70、[GPC3]H1_L1.71、[GPC3]H1_L1.72、[GPC3]H1_L1.73、[GPC3]H1.1_L1、[GPC3]H1.1_L1.1、[GPC3]H1.1_L1.2、[GPC3]H1.1_L1.3、[GPC3]H1.1_L1.4、[GPC3]H1.1_L1.5、[GPC3]H1.1_L1.6、[GPC3]H1.1_L1.7、[GPC3]H1.1_L1.8、[GPC3]H1.1_L1.9、[GPC3]H1.1_L1.10、[GPC3]H1.1_L1.16、[GPC3]H1.1_L1.23、[GPC3]H1.1_L1.29、[GPC3]H1.1_L1.31、[GPC3]H1.1_L1.65、[GPC3]H1.1_L1.66、L1.67、[GPC3]H1.1_L1.68、[GPC3]H1.1_L1.70、[GPC3]H1.1_L1.71、[GPC3]H1.1_L1.72、[GPC3]H1.1_L1.73、[GPC3]H1.2_L1、[GPC3]H1.2_L1.1、[GPC3]H1.2_L1.2、[GPC3]H1.2_L1.3、[GPC3]H1.2_L1.4、[GPC3]H1.2_L1.5、[GPC3]H1.2_L1.6、[GPC3]H1.2_L1.7、[GPC3]H1.2_L1.8、[GPC3]H1.2_L1.9、[GPC3]H1.2_L1.10、[GPC3]H1.2_L1.16、[GPC3]H1.2_L1.23、[GPC3]H1.2_L1.29、[GPC3]H1.2_L1.31、[GPC3]H1.2_L1.65、[GPC3]H1.2_L1.66、[GPC3]H1.2_L1.67、[GPC3]H1.2_L1.68、[GPC3]H1.2_L1.70、[GPC3]H1.2_L1.71、[GPC3]H1.2_L1.72、[GPC3]H1.2_L1.73、[GPC3]H1.3_L1、[GPC3]H1.3_L1.1、[GPC3]H1.3_L1.2、[GPC3]H1.3_L1.3、[GPC3]H1.3_L1.4、[GPC3]H1.3_L1.5、[GPC3]H1.3_L1.6、[GPC3]H1.3_L1.7、[GPC3]H1.3_L1.8、[GPC3]H1.3_L1.9、[GPC3]H1.3_L1.10、[GPC3]H1.3_L1.16、[GPC3]H1.3_L1.23、[GPC3]H1.3_L1.29、[GPC3]H1.3_L1.31、[GPC3]H1.3_L1.65、[GPC3]H1.3_L1.66、[GPC3]H1.3_L1.67、[GPC3]H1.3_L1.68、[GPC3]H1.3_L1.70、[GPC3]H1.3_L1.71、[GPC3]H1.3_L1.72、[GPC3]H1.3_L1.73、[GPC3]H1.4_L1、[GPC3]H1.4_L1.1、[GPC3]H1.4_L1.2、[GPC3]H1.4_L1.3、[GPC3]H1.4_L1.4、[GPC3]H1.4_L1.5、[GPC3]H1.4_L1.6、[GPC3]H1.4_L1.7、[GPC3]H1.4_L1.8、[GPC3]H1.4_L1.9、[GPC3]H1.4_L1.10、[GPC3]H1.4_L1.16、[GPC3]H1.4_L1.23、[GPC3]H1.4_L1.29、[GPC3]H1.4_L1.31、[GPC3]H1.4_L1.65、[GPC3]H1.4_L1.66、[GPC3]H1.4_L1.67、[GPC3]H1.4_L1.68、[GPC3]H1.4_L1.70、[GPC3]H1.4_L1.71、[GPC3]H1.4_L1.72和[GPC3]H1.4_L1.73或它们的变体。
在特定实施方案中，VH/VL对选自由[GPC3]H1.1_L1.16和[GPC3]H1.1_L1.69或它们的变体组成的组。
H.本发明的特定实施方案
本发明具体提供了结合CD3和GPC3的1+1和2+1形式。某些实施方案包括XENP38086(XENP34920的Xtend类似物，意味着它们具有相同的序列，除了Xtend类似物在每个Fc结构域上包括428L/434S)、XENP38087(XENP36935的Xtend类似物，同上)和XENP38232(XENP37625的Xtend类似物，同上)。
1.1+1形式
在特定的1+1形式实施方案中，αGPC3 ABD是Fab并具有VH/VL对[GPC3]H1.1_L1.16，并且αCD3 ABD是选自由以下组成的组的scFv：抗CD3 H1.30_L1.47、抗CD3 H1.32_L1.47、抗CD3 H1.89_L1.47、抗CD3 H1.90_L1.47、抗CD3 H1.33_L1.47、抗CD3 H1.31_L1.47、抗CD3 L1.47_H1.30、抗CD3 L1.47_H1.30、抗CD3 L1.47_H1.32、抗CD3 L1.47_H1.89、抗CD3 L1.47_H1.90、抗CD3 L1.47_H1.33和抗CD3 L1.47_H1.31。
在特定的1+1形式实施方案中，αGPC3 ABD是Fab并具有VH/VL对[GPC3]H1.1_L1.69，并且αCD3 ABD是选自由以下组成的组的scFv：抗CD3 H1.30_L1.47、抗CD3 H1.32_L1.47、抗CD3 H1.89_L1.47、抗CD3 H1.90_L1.47、抗CD3 H1.33_L1.47、抗CD3 H1.31_L1.47、抗CD3 L1.47_H1.30、抗CD3 L1.47_H1.30、抗CD3 L1.47_H1.32、抗CD3 L1.47_H1.89、抗CD3 L1.47_H1.90、抗CD3 L1.47_H1.33和抗CD3 L1.47_H1.31。
可用于许多应用的特定实施方案包括图16和图17中列出的那些，包括但不限于XENP21971、XENP34364、XENP34365、XENP34367、XENP34368、XENP35843、XENP36140、XENP36931、XENP36932、XENP36933、XENP36934、XENP36935、XENP36936、XENP36937、XENP36938、XENP36939、XENP36941和XENP38087。
2. 2+1形式
在特定的2+1形式实施方案中，αGPC3 ABD是Fab并具有VH/VL对[GPC3]H1.1_L1.16，并且αCD3 ABD是选自由以下组成的组的scFv：抗CD3 H1.30_L1.47、抗CD3 H1.32_L1.47、抗CD3 H1.89_L1.47、抗CD3 H1.90_L1.47、抗CD3 H1.33_L1.47、抗CD3 H1.31_L1.47、抗CD3 L1.47_H1.30、抗CD3 L1.47_H1.30、抗CD3 L1.47_H1.32、抗CD3 L1.47_H1.89、抗CD3 L1.47_H1.90、抗CD3 L1.47_H1.33和抗CD3 L1.47_H1.31。
在特定的2+1形式实施方案中，αGPC3 ABD是Fab并具有VH/VL对[GPC3]H1.1_L1.69，并且αCD3 ABD是选自由以下组成的组的scFv：抗CD3 H1.30_L1.47、抗CD3 H1.32_L1.47、抗CD3 H1.89_L1.47、抗CD3 H1.90_L1.47、抗CD3 H1.33_L1.47、抗CD3 H1.31_L1.47、抗CD3 L1.47_H1.30、抗CD3 L1.47_H1.30、抗CD3 L1.47_H1.32、抗CD3 L1.47_H1.89、抗CD3 L1.47_H1.90、抗CD3 L1.47_H1.33和抗CD3 L1.47_H1.31。
可用于许多应用的特定实施方案包括图18、图19、图20和图21中列出的那些，包括但不限于XENP33744、XENP33745、XENP27259、XENP33746、XENP34919、XENP34920、XENP34921、XENP34922、XENP34923、XENP35840、XENP35840、XENP37246、XENP37247、XENP38086、XENP33747、XENP35841、XENP37624、XENP37625、XENP37626、XENP38232、XENP37430、XENP37433和XENP33748。
II.本发明的核酸
本公开还提供了编码本文提供的抗GPC3抗体的核酸组合物，该抗GPC3抗体包括但不限于抗GPC3×抗CD3双特异性抗体和GPC3单特异性抗体。
如本领域的技术人员将理解的，核酸组合物将依赖于异二聚体蛋白的形式和支架。因此，举例来说，当所述形式需要三种氨基酸序列(如1+1Fab-scFv-Fc形式(例如第一氨基酸单体包含Fc结构域和scFv，第二氨基酸单体包含重链和轻链))时，可以将三种核酸序列并入一种或多种表达载体中供表达。类似地，一些形式(例如，图44中所公开的双scFv形式)仅需要两种核酸；同样，该两种核酸可以放入一个或两个表达载体中。
如所属领域中所知，取决于用于产生本文所述的异二聚抗体的宿主细胞，可以将编码本文所述的抗体的部件的核酸并入如所属领域中已知的表达载体中。通常，核酸可操作地连接到任何数量的调控元件(启动子、复制起点、可选择标记、核糖体结合位点、诱导剂等)。表达载体可以是染色体外的或整合的载体。
然后将本文所述的抗体的核酸和/或表达载体转化到本领域众所周知的任何数量的不同类型的宿主细胞中，包括哺乳动物、细菌、酵母、昆虫和/或真菌细胞，其中哺乳动物细胞(例如CHO细胞)在许多实施方案中使用。
在一些实施方案中，如果取决于形式适用的话，对每个单体进行编码的核酸和对轻链进行编码的任选核酸通常在不同或相同的启动子对照条件下各自包含在单个表达载体内。在尤其用于本文所述的抗体的实施方案中，这两种或三种核酸中的每种包含在不同表达载体上。如本文和62/025,931(特此以引用方式并入)所示，可以利用不同的载体比率驱使异二聚体形成。也就是说，令人惊讶地，虽然蛋白质包括1:1:2比率的第一单体:第二单体:轻链(在本文中具有包括异二聚抗体的三个多肽的许多实施方案的情况下)，但是这些并非得到最佳结果的比率。
通过培养包括如本领域众所周知的一个或多个表达载体的宿主细胞来制备本文所述的异二聚抗体。一旦产生，就执行传统抗体纯化步骤，包含离子交换色谱法步骤。如本文所讨论的，使两个单体的pI相差至少0.5可以通过离子交换色谱法或等电聚焦或对等电点敏感的其他方法进行分离。也就是说，包含改变每个单体的等电点(pI)的pI取代使得每个单体具有不同的pI，并且异二聚体也具有不同的pI，从而促进“1+1 Fab-scFv-Fc”和“2+1”异二聚体的等电纯化(例如，阴离子交换柱、阳离子交换柱)。这些取代还有助于测定和监测任何污染的双scFv-Fc和纯化后mAb同源二聚(例如，IEF凝胶、cIEF和分析型IEX柱)。
III.异二聚双特异性抗体的生物和生物化学功能
通常，向患有癌症的患者施用本文所述的双特异性GPC3×CD3抗体，并且以本文所述的多种方式对功效进行评估。因此，在可以进行标准功效测定时，如癌症负载、肿瘤大小、对存在或转移程度的评估等，可以也可以基于免疫状态评估来估计免疫肿瘤学治疗。这可以多种方式进行，包括体外和体内测定。
IV.治疗
一旦制备，本文所述抗体的组合物可用于许多应用，包括癌症诸如肝癌，使得本文所述抗体的异二聚组合物可用于治疗此类GPC3阳性癌症。
V.用于体内施用的抗体组合物
通过将具有期望程度的纯度的抗体与任选的药学上可接受的载剂、赋形剂或稳定剂(《雷明顿药物科学(Remington’s Pharmaceutical Sciences)》，第16版，Osol,A.编辑[1980])进行混合来制备根据本文所述的抗体使用的抗体的调配物，以供以冻干调配物或水溶液的形式进行存储。
VI.施用方式
本文所述的抗体和化疗剂根据已知的方法，如静脉内施用(作为推注(bolus)或通过在一段时间内连续输注)向受试者施用。
VII.治疗方式
在本文所述的方法中，用疗法来提供对疾病或病症的阳性治疗应答。“阳性治疗应答”旨在改善疾病或病症和/或改善与疾病或病症相关联的症状。例如，阳性治疗应答是指该疾病的以下改善中的一者或多者：(1)肿瘤细胞数量的减少；(2)肿瘤细胞死亡的增加；(3)抑制肿瘤细胞存活；(5)抑制(即，在一定程度上减缓，优选停止)肿瘤生长；(6)患者存活率增加；和(7)与疾病或病症相关联的一种或多种症状的一些缓解。
可以通过对那个疾病或病症具有特异性的标准化应答标准来确定任何给定疾病或病症的阳性治疗应答。可以使用筛选技术诸如磁共振成像(MRI)扫描、x-射线成像、计算机断层(CT)扫描、骨扫描成像、内窥镜检查和肿瘤活检取样，包含骨髓吸出(BMA)和对循环中的肿瘤细胞计数来估计针对肿瘤形态(即总体肿瘤负荷、肿瘤大小等)改变的肿瘤反应。
除了这些阳性治疗应答之外，经受疗法的受试者可能经历与疾病相关联的症状的改善的有益效果。
根据本公开的治疗包含所使用的“治疗有效量的”药物。“治疗有效量”是指以剂量计并且持续所需的时间段以实现所希望的治疗结果的有效的量。
治疗有效量可以根据如个体的疾病状态、年龄、性别和重量等因素以及药物在个体中引发期望的应答的能力而变化。治疗有效量也是其中抗体或抗体部分的任何毒性或有害作用超过治疗有益效果的量。
用于肿瘤疗法的“治疗有效量”还可以通过其稳定疾病进展的能力来测量。可以在预测人肿瘤中功效的动物模型系统中评估化合物抑制癌症的能力。
可替代地，通过熟练的从业者已知的体外测定，组合物的这种特性可以通过检验化合物抑制肿瘤生长或诱导凋亡的能力来评估。治疗有效量的治疗化合物可以减小肿瘤大小或以其他方式减轻受试者的症状。本领域的普通技术人员将能够基于如受试者的大小、受试者症状的严重程度和特定的组合物或所选择的施用途径这种因素确定这种量。
调整剂量方案以提供最佳的期望应答(例如，治疗应答)。举例来说，可以施用单次推注，可以随时间施用几个分开的剂量，或者可以根据治疗情况的紧急程度按比例减少或增加剂量。为了方便施用和剂量的均匀性，肠胃外组合物可以按剂量单位调配。如本文所用，剂量单位形式是指适于作为单一剂量用于待治疗的受试者的物理离散单位；每个单元含有经计算与所需的药物载体联合产生期望的治疗效果的预定量的活性化合物。
针对本公开的剂量单位形式的规格受制于并直接取决于：(a)活性化合物的独特特性和要实现的特定治疗效果，和(b)个体敏感性对复合用于治疗的此类活性化合物造成的本领域固有限制。
用于本文所述的双特异性抗体的有效剂量和剂量方案取决于待治疗的疾病或病症并且可以由本领域的技术人员确定。
用于本文所述的抗体中的治疗有效量的双特异性抗体的示例性非限制性范围是约0.1mg/kg-100mg/kg。
所有引用的参考文献通过引用以其全部内容明确地并入本文。
尽管以上为了说明的目的描述本公开的特定实施方案，但是所属领域技术人员将理解，在不脱离所附权利要求中描述的本发明的情况下，可以进行细节的许多变化。
实施例
A.实施例1：工程化αGPC3×αCD3双特异性抗体
设想了αGPC3×αCD3双特异性抗体(bsAb)的多种形式，其说明性形式在下面和图15中概述。
一种此类形式是1+1 Fab-scFv-Fc形式，所述形式包含共价附接至第一异二聚Fc结构域的单链Fv(“scFv”)、共价附接至互补的第二异二聚Fc结构域的重链可变区(VH)，以及轻链(LC)，所述轻链单独地转染，使得Fab结构域与可变重链结构域一起形成。
另一种形式是2+1 Fab2-scFv-Fc形式，所述形式包含VH结构域，所述结构域共价附接至CH1结构域，所述CH1结构域共价附接至scFv，所述scFv共价附接至第一异二聚Fc结构域(VH-CH1-scFv-Fc)；VH结构域，所述VH结构域共价附接至互补的第二异二聚Fc结构域；以及LC，所述LC单独地转染，使得Fab结构域与VH结构域一起形成。
通过以下方式生成αGPC3×αCD3 bsAb的DNA编码链：进行标准基因合成，之后进行等温克隆(Gibson装配)或亚克隆到含有融合配偶体(例如图6中描绘的结构域接头和/或图7至图8中描绘的主链)的pTT5表达载体中。将DNA转染到HEK293E细胞中以进行表达。1+1Fab-scFv-Fc形式和2+1 Fab2-scFv-Fc形式的说明性αGPC3×αCD3 bsAb的序列分别描绘在图16至图21中。
B.实施例2：工程化GPC3结合结构域
2A：鼠GPC3结合结构域的人源化
使用字符串内容优化对结合位于细胞膜附近的GPC3蛋白的GPC3的C末端肽(氨基酸524-563)的鼠克隆进行人源化(参见例如，2010年2月2日公布的美国专利号7,657,380)。人源化变体的序列在本文中称为GPC3-A并描绘在图12中。变体降低降解(例如天冬氨酸异构化和脱酰胺)倾向、调节GPC3结合亲和力和/或对高GPC3表达细胞系的选择性。图13中描绘了说明性的此类变体的序列。
2B：调整GPC3结合亲和力
人源化后，用可变轻链结构域中的单点突变对GPC3结合臂进行工程化，目的是产生GPC3结合亲和力的阶梯，其说明性序列描绘在图13中。对73个可变轻链结构域变体进行工程化，并与GPC3-A H1.1配对(参见实施例3C对GPC3-A H1.1变体的描述)。以1+1 Fab-scFv-Fc bsAb形式对GPC3-A变体进行工程化，并使用Octet(基于生物层干涉技术(BLI)的方法)测量对GPC3抗原的结合。Octet的实验步骤通常包括以下步骤：固定化(将配体捕获到生物传感器上)；缔合(将配体包被的生物传感器浸入含有分析物的孔中)；和解离(将生物传感器返回到含有缓冲液的孔中)。为了便于临床开发(例如通过在模型动物中研究治疗剂)，结合结构域对食蟹猴抗原具有交叉反应是有用的；因此，研究了与人和食蟹猴GPC3抗原的结合。将His标记的人和食蟹猴GPC3捕获在HIS1K传感器上，然后浸入多种浓度的双特异性抗体中。所得解离常数(KD)描绘在图23中。从高亲和力变体H1.1_L1.6(4nM)到中等亲和力变体H1.1_L1.16和H1.1_L1.29(分别为100nM和70nM)，到低亲和力变体H1.1_L1.31(400nM)获得了宽范围的KD值。
接下来，研究变体与细胞表面GPC3的结合。以1+1 Fab-scFv-Fc形式对说明性亲和力变体H1.1_L1.29、H1.1_L1.16和H1.1_L1.31进行工程化。将BsAb XENP36941(L1.29，70nMGPC3亲和力)、XENP35843(L1.16，100nM GPC3亲和力)和XENP36140(L1.31，400nM GPC3亲和力)与指定浓度的GPC3高HepG2细胞在4℃处孵育1小时。然后洗涤细胞，并在4℃处用二抗(通常为抗人Fc AlexaFlour647)染色1小时。再洗涤2次后，通过流式细胞术分析细胞。图24中描绘的所得结合曲线显示，细胞结合与GPC3亲和力相关，其中XENP36941(70nM可变轻链结构域)显示最紧密的结合，并且XENP36140(400nM可变轻链结构域)显示最弱的结合。
2C：工程化以除去易降解的残基
研究了人源化GPC3-A抗体的序列的易降解的残基。GPC3-A H1重链CDR2包括D52/P52a(Kabat编号)作为天冬氨酸异构化基序。此外，L1可变轻链结构域含有N28/G29(Kabat编号)作为脱酰胺基序。因此，制备了在这些残基处具有突变的文库，以研究是否可以在不影响GPC3结合的情况下消除该倾向，其结合数据描绘在图25中。可变重链变体H1.1中的D52E突变消除了天冬氨酸异构化倾向(相对于H1)，同时保持类似的GPC3结合(D52N导致结合减少，而D52Q和D52S是可接受的)。可变轻链变体L1.6中的G29T消除了脱酰胺倾向(相对于L1)，同时保持类似的GPC3结合(N28Q、N28Y、N28S和N28H显著减少结合，而G29A和G29K是可接受的)。应当注意，可能需要不同的突变以从亲和力变体中消除脱酰胺倾向，说明性变体的结合数据描绘在图26中。在L1.69变体中使用G29A突变以从L1.29变体中消除脱酰胺倾向(N28Y突变导致结合降低，而G29K也是可接受的)；并且在L1.73变体中使用G29K突变以从L1.31变体中消除脱酰胺倾向(N28Y和G29A突变导致低应答或异常应答)。本文所述变体的序列描绘在图13中。
C.实施例3：调整和优化αGPC3×αCD3 bsAb
αGPC3×αCD3 bsAb用各种亲和力调整的GPC3和CD3结合结构域以及用不同的GPC3结合价进行工程化，并如实施例1中一般描述的那样产生，以优化重定向T细胞细胞毒性(RTCC)、选择性和潜在治疗指数。
RTCC测定用于研究αGPC3×αCD3双特异性抗体(bsAb)重定向CD3+效应T细胞以破坏表达GPC3的细胞系的潜力。RTCC测定通常使用HepG2细胞(肝细胞癌系)作为GPC3高靶细胞、Huh7细胞(也是肝细胞癌系)作为GPC3中等靶细胞和/或HEK293细胞作为GPC3低靶细胞(肿瘤环境外细胞的替代物)来进行。使用两种重定向T细胞细胞毒性(RTCC)测定的方法：基于流式细胞术和基于乳酸脱氢酶(LDH)。对于基于流式细胞术的RTCC测定，将靶细胞与人PBMC和测试品一起以指定的效应物与靶细胞比率在37℃处孵育。孵育后，将细胞在室温下用Aqua Zombie染料染色15分钟。然后洗涤细胞并用针对细胞表面标志物的抗体染色，并通过流式细胞术分析。在CSFE+靶细胞上使用Zombie Aqua染色测定RTCC的诱导；以及通过淋巴细胞上的CD107a、CD25和CD69表达来测定T细胞的活化和脱粒。对于基于LDH的RTCC测定，将细胞和指定浓度的测试品在平底96孔板中以200ul的总体积在37℃处孵育48小时或72小时。然后根据其方案使用Promega CytoTox-one试剂盒使细胞裂解并与底物混合。使用Wallac机器读取板。V-PLEX促炎组1人试剂盒用于测量细胞因子。还应该指出的是，数据集中的一些数据集来自同一个实验，因为同时探索了几种工程化方法。
在本节中，还利用基于如WO 2016/047722中公开的αGPC3×αCD3 bsAb和图22中描绘的序列的比较物bsAb XENP31308来确定本发明的新型bsAb的基准。如上文通常所述，在RTCC测定中表征XENP31308。图27中描绘的数据显示，在10:1的效应物:靶标比率下，XENP31308在高GPC3和低GPC3表达细胞系上诱导有效的RTCC和细胞因子分泌。在另一个利用1:1效应物:靶标比率数据的实验中，如图28所示，XENP31308在低GPC3表达细胞系HEK293存在的情况下几乎不诱导RTCC，但仍然有效地诱导细胞因子分泌。由于GPC3低细胞系是健康组织的替代物，因此在低GPC3表达细胞系存在的情况下保持很少甚至没有杀伤和细胞因子释放是重要的，因为其可能在临床环境中转化为较低毒性和细胞因子风暴。对GPC3低细胞系的强杀伤将表明体内在靶非组织杀伤的可能性，这可能引起不期望的毒性。
3A：研究结合不同GPC3表位的GPC3结合结构域的影响
GPC3是膜结合的并且由α亚基和β亚基组成。α亚基(残基25-358)可以被裂解并作为可溶性GPC3释放，而β亚基仍附着于细胞膜。如实施例2A中所述，GPC3结合结构域GPC3-A结合GPC3的C末端残基524-563，GPC3是β亚基的一部分。另外的GPC3结合结构域已被描述为结合β亚基或α亚基的N末端残基359-524。为了研究与不同GPC3表位结合的效果，用结合不同GPC3表位的不同GPC3结合域对具有CD3高的1+1形式或具有CD3高-Int编号1scFv的2+1形式的αGPC3×αCD3 bsAb进行工程化。使用bsAb和HepG2细胞(10:1效应物:靶标比率)进行RTCC测定。图29中的数据(描绘如通过诱导IFNγ释放所指示的bsAb的活性)显示每种另外的表位在诱导T细胞活性方面不如GPC3-A有效。虽然一些差异可能是由于结合亲和力(克隆之间)或亲合力(形式之间)的差异，但GPC3表位很可能有助于效力降低。
3B：研究GPC3结合亲合力的影响
假设具有对GPC3的二价结合的2+1 Fab2-scFv-Fc形式的bsAb由于来自两个结合结构域的亲合力的改善而可用于以较低亲和力结合结构域实现较高效力。该形式的亲合力益处可以赋予对具有更高靶标表达的细胞系的选择性，降低体内在靶非组织(例如表达低水平GPC3的健康组织)效应的可能性。另外，体内可能存在高水平的可溶性GPC3，可能充当GPC3靶向药物的抗原沉没。与二价GPC3结合偶联的较低的GPC3结合亲和力可以通过优选结合具有比可溶性抗原高的抗原密度的细胞来帮助克服沉没。因此，研究了1+1 Fab-scFv-Fc形式、2+1 Fab2-scFv-Fc形式和传统单特异性二价形式的αGPC3×αCD3双特异性抗体的细胞结合。将GPC3-A可变轻链结构域L1.16(具有100nM的GPC3结合亲和力)和L1.31(具有400nM的GPC3结合亲和力)工程化成1+1 Fab-scFv-Fc形式、2+1 Fab2-scFv-Fc(VL/VH)和二价单特异性IgG1形式。将测试品与指定浓度的GPC3高HepG2细胞一起孵育，洗涤，用二抗染色，再次洗涤，并通过如上所述的流式细胞术分析。如图30所示，与1+1 Fab-scFv-Fc形式相比，由2+1 Fab2-scFv-Fc(VL/VH)形式赋予的亲合力改善了结合，达到与标准二价IgG相似的水平。另外，较低亲和力的L1.31克隆比1+1 Fab-scFv-Fc更显著地显示这种改善，表明较低的结合亲和力产生更多对亲合力和结合价的依赖性。
3C：研究变体CD3结合结构域对RTCC的影响
为了研究CD3结合亲和力的影响，以1+1 Fab-scFv-Fc形式和2+1 Fab2-scFv-Fc形式用对GPC3具有100nM或400nM结合亲和力的CD3高scFv、CD3高-Int编号1scFv、CD3高-Int编号2scFv和CD3中间体scFv和GPC3-A变体产生αGPC3×αCD3 bsAb，并在如上所述进行的基于流动的RTCC中使用10:1E:T比率在GPC3高HepG2靶细胞上以48小时孵育时间进行研究。图31A和图32A中绘制的数据(分别针对1+1形式和2+1形式的bsAb)表明，亲和力工程化的αGPC3×αCD3 bsAb对GPC3高HepG2细胞表现出一定范围的效力，从高(XENP33744具有5nM CD3臂和2+1形式，EC50值为62.63pg/ml)到低(XENP27259具有30nM CD3臂，1+1形式，EC50值为19920pg/ml)。双特异性抗体还以与其效力相关的方式诱导IFNγ的释放(如图31B和图32B中所描绘)和T细胞活化(如由活化标志物诸如CD69和107a的表达所指示；数据未示出)。值得注意的是，与在2+1 Fab2-scFv-Fc形式相比，将1+1 Fab-scFv-Fc形式的CD3结合亲和力从CD3高失调到CD3高-Int编号1在诱导细胞因子释放方面提供大得多的效力降低。然而，在2+1 Fab2-scFv-Fc形式中，用CD3高-Int编号2和CD3中间体使CD3结合亲和力失调仍导致诱导细胞因子释放方面的效力降低。
3D：研究亲和力失调的GPC3结合结构域对RTCC的影响
在另一个实验中，研究了如实施例2中所述的一组αGPC3×αCD3 bsAb的GPC3结合域中的工程化亲和力降低对重定向CD3+效应T细胞的能力的影响。如上所述，使用GPC3中等Huh7作为靶细胞，与指定浓度的测试品和PBMC效应细胞以10:1E:T比率混合进行48小时孵育时间的基于LDH的RTCC测定。图33显示XENP37625(具有可变轻链结构域L1.69，70nM GPC3亲和力)、XENP37624(具有可变轻链结构域L1.16，100nm GPC3亲和力)和XENP37626(具有可变轻链结构域L1.73，400nM GPC3亲和力)各自表现出大致与其相应亲和力一致的降低的杀伤效力和IFNγ分泌。
3E：研究αGPC3×αCD3 bsAb在具有不同GPC3表达水平的细胞系上诱导RTCC的能力
在靶非肿瘤毒性和细胞因子释放综合征可能在患者中导致严重的副作用；因此，重要的是调整本发明的bsAb以避免在表达低水平GPC3的健康组织存在的情况下造成杀伤和诱导细胞因子释放。
因此，基于上述各种观察结果，对另外的αGPC3×αCD3 bsAb进行工程化、生产和研究以鉴定具有最大治疗潜力和最小毒性潜力的bsAb。为此，研究了调节GPC3结合亲和力、GPC3结合价和CD3结合亲和力对双特异性抗体对具有高表达和低表达的细胞系的选择性的影响。
将HepG2(GPC3高)和HEK293(GPC3低)细胞各自与人PBMC(效应物与靶细胞的比率为1:1)和指定浓度的测试品一起在37℃处孵育72小时。图34和图35中描绘了描绘RTCC的诱导和细胞因子分泌的数据。与上述一致，双特异性抗体在GPC3高HepG2细胞存在的情况下显示出诱导RTCC和细胞因子释放的一系列效力。值得注意的是，在GPC3低HEK293细胞存在的情况下，每种双特异性抗体显示出很少甚至没有RTCC的诱导和细胞因子释放。
3F：使用Incucyte上的2D RTCC对αGPC3×αCD3 bsAb的进一步表征
利用不同的系统(Incucyte上的2D RTCC)研究了新型的αGPC3×αCD3 bsAb和比较物分子XENP31308。将指定浓度的所示测试品以10:1或1:1效应物:靶标比与HepG2或Huh7细胞和T细胞一起孵育。图36至图38中描绘了描绘RTCC的数据。在10:1的效应物:靶标(HepG2)比率下，bsAb XENP34920、XENP37430、XENP37625和XENP37624显示出与比较物XENP31308类似的效力(EC50小于100ng/ml)；其他bsAb XENP35843、XENP36935、XENP37433和XENP37626的效力低得多，但能够在更高浓度下实现有效杀伤，并且XENP36939没有显示任何杀伤。值得注意的是，在较低密度Huh7和较低效应物:靶标比率下，本发明的几种bsAb(例如XENP34920、XENP36935和XENP37625)与XENP31308比较物相比在EC50方面显示出大得多的差异，表明有可能提高治疗指数。另外，当用浓度为10μg/ml的测试品以10:1E:T比率处理GPC3高HepG2和GPC3中等Huh7靶细胞并在24小时至144小时范围内的不同时间点观察时，观察到类似的结果。如图39至图40中所描绘，包含XENP34920、XENP37430、XENP36935、XENP37624和XENP37625的亲和力失调的αGPC3×αCD3 bsAb在抑制HepG2和Huh7靶细胞中随时间推移的肿瘤生长方面是有效的，并且它们的功效非常类似于XENP31308的功效。
3G：使用3D球体RTCC模型对αGPC3×αCD3 bsAb的进一步表征
另外的RTCC系统用于进一步研究亲和力失调的αGPC3×αCD3 bsAb。在该系统中，靶肿瘤细胞以3D球体形式生长，与在平坦表面上以单层生长的细胞相比，该球体形式在生理上更类似于体内肿瘤。在该实验中，接种1,000个HepG2细胞(倍增时间为24小时)并给予72小时-96小时生长，然后添加40,000个PBMC(导致E:T比率为约3:1)以及浓度为10ug/ml的指示bsAb。每个信号(肿瘤细胞或免疫细胞)的强度在不同时间点对每个孔进行积分，并且该数据描绘在图41至图42中。图43另外示出了对肿瘤细胞和PBMC拍摄的摄影图象。仅用PBS处理，肿瘤球体和聚集在它们周围的PBMC随时间推移保持不变，而当用αGPC3×αCD3 bsAb处理时，PBMC显著增殖(如图42中定量描绘的)，并且肿瘤细胞被破坏(如图41中定量描绘的)。除XENP36939外，所有αGPC3×αCD3 bsAb在144小时后显示100％功效。
3D球体模型在具有较低亲和力的高-Int编号2CD3结合结构域的测试品中也产生了意料不到的结果。通常，对于2D模型中的2+1bsAb，高-Int编号1结合结构域和高-Int编号2结合结构域之间的CD3亲和力差异导致大约10倍的效力差异，诸如图38中可见的。然而，在该3D模型中，均具有相同的100nM GPC3结合结构域的XENP34920和XENP37624，但具有高-Int编号1CD3结合结构域的XENP34920和具有高-Int编号2结合结构域的XENP37624显示非常相似的效力曲线。如图41所示，该3D模型的意料不到的结果(其应更接近地模拟体内模型)提供了关于在该情况下较弱CD3结合物的效力的有用见解。
D.实施例4：鉴定具有最佳选择性和治疗指数的αGPC3×αCD3 bsAb
基于上述体外实验，选择几种bsAb用于进一步体内分析。这些抗体用Xtend Fc(M428L/N434S)进一步工程化以提高血清半衰期，图17、图19和图20中描绘的说明性序列为XENP38086(XENP34920的Xtend类似物)、XENP38087(XENP36935的Xtend类似物)和XENP38232(XENP37625的Xtend类似物)。
1. 4A：食蟹猴体内毒性研究
计划对食蟹猴进行研究，以研究体外改善(即GPC高相对于GPC低靶细胞的选择性，以及在GPC低细胞存在的情况下细胞因子释放的减少)是否转化为体内环境中的安全性改善。在1期剂量递增研究中，对动物(n＝1)静脉内给予1X、3X、10X、30X和60X剂量的XENP38086、XENP38087或XENP38232。抽取血液以确定IL-6浓度作为细胞因子释放综合征的指标。可以处死动物以研究另外的毒性迹象。
序列表
<110> XENCOR股份有限公司（XENCOR, INC.）
<120> 结合CD3和GPC3的异二聚抗体
<130> 067461-5282-WO
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<150> 63/173,127
<151> 2021-04-09
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<223> 人工序列的描述：合成肽
<220>
<223> 有关替代和优选实施方案的详细说明，请参见所提交的说明书
<400> 2
Gly Gly Gly Gly Ser
1 5
<210> 3
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> 有关替代和优选实施方案的详细说明，请参见所提交的说明书
<400> 3
Gly Ser Gly Gly Ser
1 5
<210> 4
<211> 4
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> 有关替代和优选实施方案的详细说明，请参见所提交的说明书
<400> 4
Gly Gly Gly Ser
1
<210> 5
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> 结构域接头
<400> 5
Gly Gly Gly Gly Ser
1 5
<210> 6
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> cFv接头
<400> 6
Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly
1 5 10 15
Lys Pro Gly Ser
20
<210> 7
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> 带正电荷的scFv接头Whitlow接头
<400> 7
Gly Ser Thr Ser Gly Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr
1 5 10 15
Lys Gly
<210> 8
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> 带正电荷的scFv接头6paxA_1（+A）
<400> 8
Ile Arg Pro Arg Ala Ile Gly Gly Ser Lys Pro Arg Val Ala
1 5 10
<210> 9
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> 带正电荷的scFv接头+B
<400> 9
Gly Lys Gly Gly Ser Gly Lys Gly Gly Ser Gly Lys Gly Gly Ser
1 5 10 15
<210> 10
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> 带正电荷的scFv接头+C
<400> 10
Gly Gly Lys Gly Ser Gly Gly Lys Gly Ser Gly Gly Lys Gly Ser
1 5 10 15
<210> 11
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> 带正电荷的scFv接头+D
<400> 11
Gly Gly Gly Lys Ser Gly Gly Gly Lys Ser Gly Gly Gly Lys Ser
1 5 10 15
<210> 12
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> 带正电荷的scFv接头+E
<400> 12
Gly Lys Gly Lys Ser Gly Lys Gly Lys Ser Gly Lys Gly Lys Ser
1 5 10 15
<210> 13
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> 带正电荷的scFv接头+F
<400> 13
Gly Gly Gly Lys Ser Gly Gly Lys Gly Ser Gly Lys Gly Gly Ser
1 5 10 15
<210> 14
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> 带正电荷的scFv接头+G
<400> 14
Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser
1 5 10 15
<210> 15
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> 带正电荷的scFv接头+H
<400> 15
Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly
1 5 10 15
Lys Pro Gly Ser
20
<210> 16
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> 带正电荷的scFv接头+I
<400> 16
Gly Lys Gly Lys Ser Gly Lys Gly Lys Ser Gly Lys Gly Lys Ser Gly
1 5 10 15
Lys Gly Lys Ser
20
<210> 17
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> 带负电荷的scFv接头Gly-Ser 20
<400> 17
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
1 5 10 15
Gly Gly Gly Ser
20
<210> 18
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> 带负电荷的scFv接头3hsc_2（-A）
<400> 18
Ser Thr Ala Gly Asp Thr His Leu Gly Gly Glu Asp Phe Asp
1 5 10
<210> 19
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> 带负电荷的scFv接头-B
<400> 19
Gly Glu Gly Gly Ser Gly Glu Gly Gly Ser Gly Glu Gly Gly Ser
1 5 10 15
<210> 20
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> 带负电荷的scFv接头-C
<400> 20
Gly Gly Glu Gly Ser Gly Gly Glu Gly Ser Gly Gly Glu Gly Ser
1 5 10 15
<210> 21
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> 带负电荷的scFv接头-D
<400> 21
Gly Gly Gly Glu Ser Gly Gly Gly Glu Ser Gly Gly Gly Glu Ser
1 5 10 15
<210> 22
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> 带负电荷的scFv接头-E
<400> 22
Gly Glu Gly Glu Ser Gly Glu Gly Glu Ser Gly Glu Gly Glu Ser
1 5 10 15
<210> 23
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> 带负电荷的scFv接头-F
<400> 23
Gly Gly Gly Glu Ser Gly Gly Glu Gly Ser Gly Glu Gly Gly Ser
1 5 10 15
<210> 24
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> 带负电荷的scFv接头-G
<400> 24
Gly Glu Gly Glu Ser Gly Glu Gly Glu Ser Gly Glu Gly Glu Ser Gly
1 5 10 15
Glu Gly Glu Ser
20
<210> 25
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> cFv接头
<400> 25
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
1 5 10 15
<210> 26
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> cFv接头
<400> 26
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
1 5 10 15
Gly Gly Gly Ser
20
<210> 27
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> cFv接头
<400> 27
Gly Ser Thr Ser Gly Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr
1 5 10 15
Lys Gly
<210> 28
<211> 19
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> cFv接头
<400> 28
Pro Arg Gly Ala Ser Lys Ser Gly Ser Ala Ser Gln Thr Gly Ser Ala
1 5 10 15
Pro Gly Ser
<210> 29
<211> 19
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> cFv接头
<400> 29
Gly Thr Ala Ala Ala Gly Ala Gly Ala Ala Gly Gly Ala Ala Ala Gly
1 5 10 15
Ala Ala Gly
<210> 30
<211> 19
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> cFv接头
<400> 30
Gly Thr Ser Gly Ser Ser Gly Ser Gly Ser Gly Gly Ser Gly Ser Gly
1 5 10 15
Gly Gly Gly
<210> 31
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> 结构域接头
<400> 31
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
1 5 10
<210> 32
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> 结构域接头
<400> 32
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
1 5 10 15
<210> 33
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> 结构域接头
<400> 33
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
1 5 10 15
Gly Gly Gly Ser
20
<210> 34
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> 结构域接头
<400> 34
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
1 5 10 15
Gly Gly Gly Ser Gly Gly Gly Gly Ser
20 25
<210> 35
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 结构域接头
<400> 35
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
1 5 10 15
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
20 25 30
<210> 36
<211> 35
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 结构域接头
<400> 36
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
1 5 10 15
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
20 25 30
Gly Gly Ser
35
<210> 37
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> 结构域接头
<400> 37
Gly Gly Gly Gly Ala
1 5
<210> 38
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> 结构域接头
<400> 38
Gly Gly Gly Gly Ala Gly Gly Gly Gly Ala
1 5 10
<210> 39
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> 结构域接头
<400> 39
Gly Gly Gly Gly Ala Gly Gly Gly Gly Ala Gly Gly Gly Gly Ala
1 5 10 15
<210> 40
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> 结构域接头
<400> 40
Gly Gly Gly Gly Ala Gly Gly Gly Gly Ala Gly Gly Gly Gly Ala Gly
1 5 10 15
Gly Gly Gly Ala
20
<210> 41
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> 结构域接头
<400> 41
Gly Gly Gly Gly Ala Gly Gly Gly Gly Ala Gly Gly Gly Gly Ala Gly
1 5 10 15
Gly Gly Gly Ala Gly Gly Gly Gly Ala
20 25
<210> 42
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 结构域接头
<400> 42
Gly Gly Gly Gly Ala Gly Gly Gly Gly Ala Gly Gly Gly Gly Ala Gly
1 5 10 15
Gly Gly Gly Ala Gly Gly Gly Gly Ala Gly Gly Gly Gly Ala
20 25 30
<210> 43
<211> 35
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 结构域接头
<400> 43
Gly Gly Gly Gly Ala Gly Gly Gly Gly Ala Gly Gly Gly Gly Ala Gly
1 5 10 15
Gly Gly Gly Ala Gly Gly Gly Gly Ala Gly Gly Gly Gly Ala Gly Gly
20 25 30
Gly Gly Ala
35
<210> 44
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 结构域接头30AA-接头
<400> 44
Asp Pro Ala Leu Val His Gln Arg Pro Ala Pro Pro Gly Gly Gly Gly
1 5 10 15
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
20 25 30
<210> 45
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> 结构域接头
<400> 45
Gly Lys Pro Gly Ser
1 5
<210> 46
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> 结构域接头
<400> 46
Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly
1 5 10 15
Lys Pro Gly Ser Gly Lys Pro Gly Ser
20 25
<210> 47
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 结构域接头
<400> 47
Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly
1 5 10 15
Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser
20 25 30
<210> 48
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> 结构域接头
<400> 48
Gly Gly Gly Glu Ser
1 5
<210> 49
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> 结构域接头“半铰链”
<400> 49
Lys Thr His Thr Cys Pro Pro Cys Pro
1 5
<210> 50
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> 结构域接头“全铰链C220S变体”
<400> 50
Glu Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro
1 5 10 15
<210> 51
<211> 19
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> 结构域接头“挠曲半铰链”
<400> 51
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Lys Thr His Thr Cys Pro
1 5 10 15
Pro Cys Pro
<210> 52
<211> 19
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> 结构域接头“带电荷的半铰链1”
<400> 52
Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Lys Thr His Thr Cys Pro
1 5 10 15
Pro Cys Pro
<210> 53
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> 结构域接头“带电荷的半铰链2”
<400> 53
Gly Lys Pro Gly Ser Lys Thr His Thr Cys Pro Pro Cys Pro
1 5 10
<210> 54
<211> 329
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 1+1 Fab-scFv-Fc主链1 Fab-Fc侧
<400> 54
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys
1 5 10 15
Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr
65 70 75 80
Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys Val Asp Lys
85 90 95
Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys
100 105 110
Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
115 120 125
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
130 135 140
Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
145 150 155 160
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
165 170 175
Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
180 185 190
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
195 200 205
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
210 215 220
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met
225 230 235 240
Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly Phe Tyr Pro
245 250 255
Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro Glu Asn Asn
260 265 270
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
275 280 285
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln Gly Asp Val
290 295 300
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
305 310 315 320
Lys Ser Leu Ser Leu Ser Pro Gly Lys
325
<210> 55
<211> 231
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 1+1 Fab-scFv-Fc主链1 scFv-Fc侧
<400> 55
Glu Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala
1 5 10 15
Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
20 25 30
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
35 40 45
Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp
50 55 60
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr
65 70 75 80
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
85 90 95
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu
100 105 110
Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
115 120 125
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys
130 135 140
Asn Gln Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
145 150 155 160
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
165 170 175
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
180 185 190
Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser
195 200 205
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
210 215 220
Leu Ser Leu Ser Pro Gly Lys
225 230
<210> 56
<211> 329
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 1+1 Fab-scFv-Fc主链2 Fab-Fc侧
<400> 56
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys
1 5 10 15
Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr
65 70 75 80
Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys Val Asp Lys
85 90 95
Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys
100 105 110
Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
115 120 125
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
130 135 140
Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
145 150 155 160
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
165 170 175
Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
180 185 190
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
195 200 205
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
210 215 220
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met
225 230 235 240
Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly Phe Tyr Pro
245 250 255
Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro Glu Asn Asn
260 265 270
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
275 280 285
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln Gly Asp Val
290 295 300
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
305 310 315 320
Lys Ser Leu Ser Leu Ser Pro Gly Lys
325
<210> 57
<211> 231
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 1+1 Fab-scFv-Fc主链2 scFv-Fc侧
<400> 57
Glu Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala
1 5 10 15
Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
20 25 30
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
35 40 45
Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp
50 55 60
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr
65 70 75 80
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
85 90 95
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu
100 105 110
Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
115 120 125
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys
130 135 140
Asn Gln Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
145 150 155 160
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
165 170 175
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
180 185 190
Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser
195 200 205
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
210 215 220
Leu Ser Leu Ser Pro Gly Lys
225 230
<210> 58
<211> 329
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 1+1 Fab-scFv-Fc主链3 Fab-Fc侧
<400> 58
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys
1 5 10 15
Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr
65 70 75 80
Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys Val Asp Lys
85 90 95
Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys
100 105 110
Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
115 120 125
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
130 135 140
Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
145 150 155 160
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
165 170 175
Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
180 185 190
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
195 200 205
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
210 215 220
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met
225 230 235 240
Thr Lys Asn Gln Val Ser Leu Thr Cys Glu Val Ser Gly Phe Tyr Pro
245 250 255
Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro Glu Asn Asn
260 265 270
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
275 280 285
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln Gly Asp Val
290 295 300
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
305 310 315 320
Lys Ser Leu Ser Leu Ser Pro Gly Lys
325
<210> 59
<211> 231
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 1+1 Fab-scFv-Fc主链3 scFv-Fc侧
<400> 59
Glu Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala
1 5 10 15
Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
20 25 30
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
35 40 45
Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp
50 55 60
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr
65 70 75 80
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
85 90 95
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu
100 105 110
Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
115 120 125
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys
130 135 140
Asn Gln Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
145 150 155 160
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
165 170 175
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
180 185 190
Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser
195 200 205
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
210 215 220
Leu Ser Leu Ser Pro Gly Lys
225 230
<210> 60
<211> 329
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 1+1 Fab-scFv-Fc主链4 Fab-Fc侧
<400> 60
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys
1 5 10 15
Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr
65 70 75 80
Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys Val Asp Lys
85 90 95
Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys
100 105 110
Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
115 120 125
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
130 135 140
Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
145 150 155 160
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
165 170 175
Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
180 185 190
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
195 200 205
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
210 215 220
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met
225 230 235 240
Thr Glu Asn Glu Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
245 250 255
Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro Glu Asn Asn
260 265 270
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
275 280 285
Tyr Ser Lys Leu Glu Val Asp Lys Ser Arg Trp Glu Gln Gly Asp Val
290 295 300
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
305 310 315 320
Lys Ser Leu Ser Leu Ser Pro Gly Lys
325
<210> 61
<211> 231
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 1+1 Fab-scFv-Fc主链4 scFv-Fc侧
<400> 61
Glu Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala
1 5 10 15
Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
20 25 30
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
35 40 45
Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp
50 55 60
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr
65 70 75 80
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
85 90 95
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu
100 105 110
Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
115 120 125
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys
130 135 140
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
145 150 155 160
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
165 170 175
Thr Thr Pro Pro Val Leu Asp Ser Lys Gly Ser Phe Phe Leu Tyr Ser
180 185 190
Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser
195 200 205
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
210 215 220
Leu Ser Leu Ser Pro Gly Lys
225 230
<210> 62
<211> 329
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 1+1 Fab-scFv-Fc主链5 Fab-Fc侧
<400> 62
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys
1 5 10 15
Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr
65 70 75 80
Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys Val Asp Lys
85 90 95
Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys
100 105 110
Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
115 120 125
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
130 135 140
Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
145 150 155 160
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
165 170 175
Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
180 185 190
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
195 200 205
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
210 215 220
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
225 230 235 240
Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly Phe Tyr Pro
245 250 255
Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro Glu Asn Asn
260 265 270
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
275 280 285
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln Gly Asp Val
290 295 300
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
305 310 315 320
Lys Ser Leu Ser Leu Ser Pro Gly Lys
325
<210> 63
<211> 231
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 1+1 Fab-scFv-Fc主链5 scFv-Fc侧
<400> 63
Glu Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala
1 5 10 15
Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
20 25 30
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
35 40 45
Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp
50 55 60
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr
65 70 75 80
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
85 90 95
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu
100 105 110
Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
115 120 125
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Gln Leu Thr Lys
130 135 140
Asn Gln Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
145 150 155 160
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
165 170 175
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
180 185 190
Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser
195 200 205
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
210 215 220
Leu Ser Leu Ser Pro Gly Lys
225 230
<210> 64
<211> 329
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 1+1 Fab-scFv-Fc主链6 Fab-Fc侧
<400> 64
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys
1 5 10 15
Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr
65 70 75 80
Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys Val Asp Lys
85 90 95
Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys
100 105 110
Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
115 120 125
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
130 135 140
Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
145 150 155 160
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
165 170 175
Glu Tyr Ala Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
180 185 190
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
195 200 205
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
210 215 220
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met
225 230 235 240
Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly Phe Tyr Pro
245 250 255
Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro Glu Asn Asn
260 265 270
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
275 280 285
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln Gly Asp Val
290 295 300
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
305 310 315 320
Lys Ser Leu Ser Leu Ser Pro Gly Lys
325
<210> 65
<211> 231
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 1+1 Fab-scFv-Fc主链6 scFv-Fc侧
<400> 65
Glu Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala
1 5 10 15
Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
20 25 30
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
35 40 45
Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp
50 55 60
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr
65 70 75 80
Ala Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
85 90 95
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu
100 105 110
Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
115 120 125
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys
130 135 140
Asn Gln Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
145 150 155 160
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
165 170 175
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
180 185 190
Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser
195 200 205
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
210 215 220
Leu Ser Leu Ser Pro Gly Lys
225 230
<210> 66
<211> 329
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 1+1 Fab-scFv-Fc主链7 Fab-Fc侧
<400> 66
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys
1 5 10 15
Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr
65 70 75 80
Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys Val Asp Lys
85 90 95
Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys
100 105 110
Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
115 120 125
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
130 135 140
Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
145 150 155 160
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
165 170 175
Glu Tyr Ser Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
180 185 190
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
195 200 205
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
210 215 220
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met
225 230 235 240
Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly Phe Tyr Pro
245 250 255
Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro Glu Asn Asn
260 265 270
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
275 280 285
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln Gly Asp Val
290 295 300
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
305 310 315 320
Lys Ser Leu Ser Leu Ser Pro Gly Lys
325
<210> 67
<211> 231
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 1+1 Fab-scFv-Fc主链7 scFv-Fc侧
<400> 67
Glu Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala
1 5 10 15
Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
20 25 30
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
35 40 45
Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp
50 55 60
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr
65 70 75 80
Ser Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
85 90 95
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu
100 105 110
Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
115 120 125
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys
130 135 140
Asn Gln Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
145 150 155 160
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
165 170 175
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
180 185 190
Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser
195 200 205
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
210 215 220
Leu Ser Leu Ser Pro Gly Lys
225 230
<210> 68
<211> 327
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 1+1 Fab-scFv-Fc主链8 Fab-Fc侧
<400> 68
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg
1 5 10 15
Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr
65 70 75 80
Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asp Thr Lys Val Asp Lys
85 90 95
Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro
100 105 110
Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
115 120 125
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
130 135 140
Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp
145 150 155 160
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Glu Phe
165 170 175
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
180 185 190
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu
195 200 205
Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
210 215 220
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys
225 230 235 240
Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly Phe Tyr Pro Ser Asp
245 250 255
Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro Glu Asn Asn Tyr Lys
260 265 270
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
275 280 285
Arg Leu Thr Val Asp Lys Ser Arg Trp Glu Glu Gly Asp Val Phe Ser
290 295 300
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
305 310 315 320
Leu Ser Leu Ser Leu Gly Lys
325
<210> 69
<211> 229
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 1+1 Fab-scFv-Fc主链8 scFv-Fc侧
<400> 69
Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe
1 5 10 15
Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
20 25 30
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
35 40 45
Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val
50 55 60
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser
65 70 75 80
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
85 90 95
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser
100 105 110
Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
115 120 125
Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Gln Met Thr Lys Asn Gln
130 135 140
Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
145 150 155 160
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
165 170 175
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu
180 185 190
Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser
195 200 205
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
210 215 220
Leu Ser Leu Gly Lys
225
<210> 70
<211> 326
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 1+1 Fab-scFv-Fc主链9 Fab-Fc侧
<400> 70
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg
1 5 10 15
Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Asn Phe Gly Thr Gln Thr
65 70 75 80
Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asp Thr Lys Val Asp Lys
85 90 95
Thr Val Glu Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro
100 105 110
Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp
115 120 125
Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
130 135 140
Val Ser His Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly
145 150 155 160
Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Glu Phe Asn
165 170 175
Ser Thr Phe Arg Val Val Ser Val Leu Thr Val Val His Gln Asp Trp
180 185 190
Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro
195 200 205
Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu
210 215 220
Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn
225 230 235 240
Gln Val Ser Leu Thr Cys Asp Val Ser Gly Phe Tyr Pro Ser Asp Ile
245 250 255
Ala Val Glu Trp Glu Ser Asp Gly Gln Pro Glu Asn Asn Tyr Lys Thr
260 265 270
Thr Pro Pro Met Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys
275 280 285
Leu Thr Val Asp Lys Ser Arg Trp Glu Gln Gly Asp Val Phe Ser Cys
290 295 300
Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu
305 310 315 320
Ser Leu Ser Pro Gly Lys
325
<210> 71
<211> 228
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 1+1 Fab-scFv-Fc主链9 scFv-Fc侧
<400> 71
Glu Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val
1 5 10 15
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
20 25 30
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
35 40 45
His Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu
50 55 60
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr
65 70 75 80
Phe Arg Val Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu Asn
85 90 95
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ala Pro
100 105 110
Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln
115 120 125
Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln Val
130 135 140
Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
145 150 155 160
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
165 170 175
Pro Met Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
180 185 190
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
195 200 205
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
210 215 220
Ser Pro Gly Lys
225
<210> 72
<211> 326
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 1+1 Fab-scFv-Fc主链10 Fab-Fc侧
<400> 72
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg
1 5 10 15
Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Asn Phe Gly Thr Gln Thr
65 70 75 80
Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asp Thr Lys Val Asp Lys
85 90 95
Thr Val Glu Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro
100 105 110
Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp
115 120 125
Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
130 135 140
Val Lys His Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly
145 150 155 160
Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Glu Phe Asn
165 170 175
Ser Thr Phe Arg Val Val Ser Val Leu Thr Val Val His Gln Asp Trp
180 185 190
Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro
195 200 205
Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu
210 215 220
Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn
225 230 235 240
Gln Val Ser Leu Thr Cys Asp Val Ser Gly Phe Tyr Pro Ser Asp Ile
245 250 255
Ala Val Glu Trp Glu Ser Asp Gly Gln Pro Glu Asn Asn Tyr Lys Thr
260 265 270
Thr Pro Pro Met Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys
275 280 285
Leu Thr Val Asp Lys Ser Arg Trp Glu Gln Gly Asp Val Phe Ser Cys
290 295 300
Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu
305 310 315 320
Ser Leu Ser Pro Gly Lys
325
<210> 73
<211> 228
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 1+1 Fab-scFv-Fc主链10 scFv-Fc侧
<400> 73
Glu Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val
1 5 10 15
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
20 25 30
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Lys
35 40 45
His Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu
50 55 60
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr
65 70 75 80
Phe Arg Val Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu Asn
85 90 95
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ala Pro
100 105 110
Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln
115 120 125
Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln Val
130 135 140
Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
145 150 155 160
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
165 170 175
Pro Met Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
180 185 190
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
195 200 205
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
210 215 220
Ser Pro Gly Lys
225
<210> 74
<211> 329
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 1+1 Fab-scFv-Fc主链11 Fab-Fc侧
<400> 74
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys
1 5 10 15
Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr
65 70 75 80
Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys Val Asp Lys
85 90 95
Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys
100 105 110
Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
115 120 125
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
130 135 140
Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
145 150 155 160
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
165 170 175
Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
180 185 190
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
195 200 205
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
210 215 220
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met
225 230 235 240
Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly Phe Tyr Pro
245 250 255
Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro Glu Asn Asn
260 265 270
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
275 280 285
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln Gly Asp Val
290 295 300
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
305 310 315 320
Lys Ser Leu Ser Leu Ser Pro Gly Lys
325
<210> 75
<211> 231
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 1+1 Fab-scFv-Fc主链11 scFv-Fc侧
<400> 75
Glu Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala
1 5 10 15
Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
20 25 30
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
35 40 45
Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp
50 55 60
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr
65 70 75 80
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
85 90 95
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu
100 105 110
Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
115 120 125
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys
130 135 140
Asn Gln Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
145 150 155 160
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
165 170 175
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
180 185 190
Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser
195 200 205
Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln Lys Ser
210 215 220
Leu Ser Leu Ser Pro Gly Lys
225 230
<210> 76
<211> 329
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 1+1 Fab-scFv-Fc主链12 Fab-Fc侧
<400> 76
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys
1 5 10 15
Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr
65 70 75 80
Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys
85 90 95
Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys
100 105 110
Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
115 120 125
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
130 135 140
Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
145 150 155 160
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
165 170 175
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
180 185 190
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
195 200 205
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
210 215 220
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met
225 230 235 240
Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ala Gly Phe Tyr Pro
245 250 255
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
260 265 270
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
275 280 285
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val
290 295 300
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
305 310 315 320
Lys Ser Leu Ser Leu Ser Pro Gly Lys
325
<210> 77
<211> 231
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 1+1 Fab-scFv-Fc主链12 scFv-Fc侧
<400> 77
Glu Arg Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Arg Pro Ala
1 5 10 15
Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
20 25 30
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
35 40 45
Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Lys Trp Tyr Val Asp
50 55 60
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr
65 70 75 80
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
85 90 95
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu
100 105 110
Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
115 120 125
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys
130 135 140
Asn Gln Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
145 150 155 160
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
165 170 175
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
180 185 190
Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser
195 200 205
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
210 215 220
Leu Ser Leu Ser Pro Gly Lys
225 230
<210> 78
<211> 329
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 2+1 Fab2-scFv-Fc主链1 Fab-Fc侧
<400> 78
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys
1 5 10 15
Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr
65 70 75 80
Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys Val Asp Lys
85 90 95
Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys
100 105 110
Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
115 120 125
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
130 135 140
Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
145 150 155 160
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
165 170 175
Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
180 185 190
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
195 200 205
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
210 215 220
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met
225 230 235 240
Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly Phe Tyr Pro
245 250 255
Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro Glu Asn Asn
260 265 270
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
275 280 285
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln Gly Asp Val
290 295 300
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
305 310 315 320
Lys Ser Leu Ser Leu Ser Pro Gly Lys
325
<210> 79
<211> 216
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 2+1 Fab2-scFv-Fc主链1 Fab-scFv-Fc侧
<400> 79
Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro
1 5 10 15
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
20 25 30
Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val
35 40 45
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln
50 55 60
Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln
65 70 75 80
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala
85 90 95
Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro
100 105 110
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr
115 120 125
Lys Asn Gln Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser
130 135 140
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr
145 150 155 160
Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr
165 170 175
Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe
180 185 190
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
195 200 205
Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 80
<211> 329
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 2+1 Fab2-scFv-Fc主链2 Fab-Fc侧
<400> 80
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys
1 5 10 15
Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr
65 70 75 80
Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys Val Asp Lys
85 90 95
Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys
100 105 110
Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
115 120 125
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
130 135 140
Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
145 150 155 160
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
165 170 175
Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
180 185 190
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
195 200 205
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
210 215 220
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met
225 230 235 240
Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly Phe Tyr Pro
245 250 255
Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro Glu Asn Asn
260 265 270
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
275 280 285
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln Gly Asp Val
290 295 300
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
305 310 315 320
Lys Ser Leu Ser Leu Ser Pro Gly Lys
325
<210> 81
<211> 216
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 2+1 Fab2-scFv-Fc主链2 Fab-scFv-Fc侧
<400> 81
Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro
1 5 10 15
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
20 25 30
Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val
35 40 45
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln
50 55 60
Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln
65 70 75 80
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala
85 90 95
Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro
100 105 110
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr
115 120 125
Lys Asn Gln Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser
130 135 140
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr
145 150 155 160
Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr
165 170 175
Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe
180 185 190
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
195 200 205
Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 82
<211> 329
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 2+1 Fab2-scFv-Fc主链3 Fab-Fc侧
<400> 82
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys
1 5 10 15
Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr
65 70 75 80
Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys Val Asp Lys
85 90 95
Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys
100 105 110
Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
115 120 125
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
130 135 140
Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
145 150 155 160
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
165 170 175
Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
180 185 190
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
195 200 205
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
210 215 220
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met
225 230 235 240
Thr Lys Asn Gln Val Ser Leu Thr Cys Glu Val Ser Gly Phe Tyr Pro
245 250 255
Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro Glu Asn Asn
260 265 270
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
275 280 285
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln Gly Asp Val
290 295 300
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
305 310 315 320
Lys Ser Leu Ser Leu Ser Pro Gly Lys
325
<210> 83
<211> 216
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 2+1 Fab2-scFv-Fc主链3 Fab-scFv-Fc侧
<400> 83
Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro
1 5 10 15
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
20 25 30
Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val
35 40 45
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln
50 55 60
Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln
65 70 75 80
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala
85 90 95
Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro
100 105 110
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr
115 120 125
Lys Asn Gln Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser
130 135 140
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr
145 150 155 160
Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr
165 170 175
Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe
180 185 190
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
195 200 205
Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 84
<211> 329
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 2+1 Fab2-scFv-Fc主链4 Fab-Fc侧
<400> 84
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys
1 5 10 15
Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr
65 70 75 80
Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys Val Asp Lys
85 90 95
Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys
100 105 110
Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
115 120 125
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
130 135 140
Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
145 150 155 160
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
165 170 175
Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
180 185 190
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
195 200 205
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
210 215 220
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met
225 230 235 240
Thr Glu Asn Glu Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
245 250 255
Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro Glu Asn Asn
260 265 270
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
275 280 285
Tyr Ser Lys Leu Glu Val Asp Lys Ser Arg Trp Glu Gln Gly Asp Val
290 295 300
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
305 310 315 320
Lys Ser Leu Ser Leu Ser Pro Gly Lys
325
<210> 85
<211> 216
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 2+1 Fab2-scFv-Fc主链4 Fab-scFv-Fc侧
<400> 85
Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro
1 5 10 15
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
20 25 30
Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val
35 40 45
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln
50 55 60
Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln
65 70 75 80
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala
85 90 95
Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro
100 105 110
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr
115 120 125
Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser
130 135 140
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr
145 150 155 160
Lys Thr Thr Pro Pro Val Leu Asp Ser Lys Gly Ser Phe Phe Leu Tyr
165 170 175
Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe
180 185 190
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
195 200 205
Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 86
<211> 329
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 2+1 Fab2-scFv-Fc主链5 Fab-Fc侧
<400> 86
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys
1 5 10 15
Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr
65 70 75 80
Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys Val Asp Lys
85 90 95
Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys
100 105 110
Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
115 120 125
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
130 135 140
Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
145 150 155 160
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
165 170 175
Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
180 185 190
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
195 200 205
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
210 215 220
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
225 230 235 240
Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly Phe Tyr Pro
245 250 255
Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro Glu Asn Asn
260 265 270
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
275 280 285
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln Gly Asp Val
290 295 300
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
305 310 315 320
Lys Ser Leu Ser Leu Ser Pro Gly Lys
325
<210> 87
<211> 216
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 2+1 Fab2-scFv-Fc主链5 Fab-scFv-Fc侧
<400> 87
Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro
1 5 10 15
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
20 25 30
Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val
35 40 45
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln
50 55 60
Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln
65 70 75 80
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala
85 90 95
Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro
100 105 110
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Gln Leu Thr
115 120 125
Lys Asn Gln Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser
130 135 140
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr
145 150 155 160
Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr
165 170 175
Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe
180 185 190
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
195 200 205
Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 88
<211> 329
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 2+1 Fab2-scFv-Fc主链6 Fab-Fc侧
<400> 88
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys
1 5 10 15
Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr
65 70 75 80
Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys Val Asp Lys
85 90 95
Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys
100 105 110
Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
115 120 125
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
130 135 140
Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
145 150 155 160
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
165 170 175
Glu Tyr Ala Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
180 185 190
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
195 200 205
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
210 215 220
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met
225 230 235 240
Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly Phe Tyr Pro
245 250 255
Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro Glu Asn Asn
260 265 270
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
275 280 285
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln Gly Asp Val
290 295 300
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
305 310 315 320
Lys Ser Leu Ser Leu Ser Pro Gly Lys
325
<210> 89
<211> 216
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 2+1 Fab2-scFv-Fc主链6 Fab-scFv-Fc侧
<400> 89
Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro
1 5 10 15
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
20 25 30
Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val
35 40 45
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln
50 55 60
Tyr Ala Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln
65 70 75 80
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala
85 90 95
Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro
100 105 110
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr
115 120 125
Lys Asn Gln Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser
130 135 140
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr
145 150 155 160
Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr
165 170 175
Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe
180 185 190
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
195 200 205
Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 90
<211> 329
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 2+1 Fab2-scFv-Fc主链7 Fab-Fc侧
<400> 90
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys
1 5 10 15
Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr
65 70 75 80
Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys Val Asp Lys
85 90 95
Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys
100 105 110
Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
115 120 125
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
130 135 140
Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
145 150 155 160
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
165 170 175
Glu Tyr Ser Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
180 185 190
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
195 200 205
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
210 215 220
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met
225 230 235 240
Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly Phe Tyr Pro
245 250 255
Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro Glu Asn Asn
260 265 270
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
275 280 285
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln Gly Asp Val
290 295 300
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
305 310 315 320
Lys Ser Leu Ser Leu Ser Pro Gly Lys
325
<210> 91
<211> 216
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 2+1 Fab2-scFv-Fc主链7 Fab-scFv-Fc侧
<400> 91
Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro
1 5 10 15
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
20 25 30
Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val
35 40 45
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln
50 55 60
Tyr Ser Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln
65 70 75 80
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala
85 90 95
Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro
100 105 110
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr
115 120 125
Lys Asn Gln Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser
130 135 140
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr
145 150 155 160
Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr
165 170 175
Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe
180 185 190
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
195 200 205
Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 92
<211> 329
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 2+1 Fab2-scFv-Fc主链8 Fab-Fc侧
<400> 92
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys
1 5 10 15
Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr
65 70 75 80
Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys Val Asp Lys
85 90 95
Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys
100 105 110
Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
115 120 125
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
130 135 140
Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
145 150 155 160
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
165 170 175
Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
180 185 190
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
195 200 205
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
210 215 220
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met
225 230 235 240
Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly Phe Tyr Pro
245 250 255
Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro Glu Asn Asn
260 265 270
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
275 280 285
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln Gly Asp Val
290 295 300
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
305 310 315 320
Lys Ser Leu Ser Leu Ser Pro Gly Lys
325
<210> 93
<211> 216
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 2+1 Fab2-scFv-Fc主链8 Fab-scFv-Fc侧
<400> 93
Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro
1 5 10 15
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
20 25 30
Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val
35 40 45
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln
50 55 60
Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln
65 70 75 80
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala
85 90 95
Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro
100 105 110
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr
115 120 125
Lys Asn Gln Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser
130 135 140
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr
145 150 155 160
Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr
165 170 175
Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe
180 185 190
Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln Lys
195 200 205
Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 94
<211> 329
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 2+1 Fab2-scFv-Fc主链9 Fab-Fc侧
<400> 94
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys
1 5 10 15
Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr
65 70 75 80
Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys
85 90 95
Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys
100 105 110
Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
115 120 125
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
130 135 140
Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
145 150 155 160
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
165 170 175
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
180 185 190
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
195 200 205
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
210 215 220
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met
225 230 235 240
Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ala Gly Phe Tyr Pro
245 250 255
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
260 265 270
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
275 280 285
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val
290 295 300
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
305 310 315 320
Lys Ser Leu Ser Leu Ser Pro Gly Lys
325
<210> 95
<211> 216
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 2+1 Fab2-scFv-Fc主链9 Fab-scFv-Fc侧
<400> 95
Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro
1 5 10 15
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
20 25 30
Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Lys Trp Tyr Val
35 40 45
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln
50 55 60
Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln
65 70 75 80
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala
85 90 95
Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro
100 105 110
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr
115 120 125
Lys Asn Gln Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser
130 135 140
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr
145 150 155 160
Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr
165 170 175
Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe
180 185 190
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
195 200 205
Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 96
<211> 107
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 恒定轻链结构域-κ
<400> 96
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
1 5 10 15
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
20 25 30
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
35 40 45
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
50 55 60
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
65 70 75 80
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
85 90 95
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
100 105
<210> 97
<211> 106
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> 恒定轻链结构域-λ
<400> 97
Gly Gln Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser
1 5 10 15
Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp
20 25 30
Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro
35 40 45
Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn
50 55 60
Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys
65 70 75 80
Ser His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val
85 90 95
Glu Lys Thr Val Ala Pro Thr Glu Cys Ser
100 105
<210> 98
<211> 254
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> CD3高-[抗CD3]_H1.30_L1.47_scFv scFv（VHVL）
<400> 98
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr
20 25 30
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp
50 55 60
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
65 70 75 80
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
85 90 95
Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro
115 120 125
Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly
130 135 140
Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly
145 150 155 160
Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr
165 170 175
Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg
180 185 190
Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg
195 200 205
Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly
210 215 220
Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser
225 230 235 240
Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
245 250
<210> 99
<211> 254
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> CD3高-[抗CD3]_H1.30_L1.47_scFv scFv（VLVH）
<400> 99
Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly
1 5 10 15
Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser
20 25 30
Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly
35 40 45
Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe
50 55 60
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala
65 70 75 80
Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn
85 90 95
His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Lys Pro
100 105 110
Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly
115 120 125
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
130 135 140
Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr
145 150 155 160
Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
165 170 175
Val Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
180 185 190
Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
195 200 205
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
210 215 220
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp
225 230 235 240
Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
245 250
<210> 100
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> CD3高-[抗CD3]_H1.30_L1.47_scFv可变重链（vh）结构域
<400> 100
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr
20 25 30
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp
50 55 60
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
65 70 75 80
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
85 90 95
Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 125
<210> 101
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3高-[抗CD3]_H1.30_L1.47_scFv vhCDR1
<400> 101
Thr Tyr Ala Met Asn
1 5
<210> 102
<211> 19
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3高-[抗CD3]_H1.30_L1.47_scFv vhCDR2
<400> 102
Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser
1 5 10 15
Val Lys Gly
<210> 103
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3高-[抗CD3]_H1.30_L1.47_scFv vhCDR3
<400> 103
His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe Ala Tyr
1 5 10
<210> 104
<211> 109
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> CD3高-[抗CD3]_H1.30_L1.47_scFv可变轻链（vl）结构域
<400> 104
Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly
1 5 10 15
Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser
20 25 30
Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly
35 40 45
Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe
50 55 60
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala
65 70 75 80
Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn
85 90 95
His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
100 105
<210> 105
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3高-[抗CD3]_H1.30_L1.47_scFv vlCDR1
<400> 105
Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn
1 5 10
<210> 106
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3高-[抗CD3]_H1.30_L1.47_scFv vlCDR2
<400> 106
Gly Thr Asn Lys Arg Ala Pro
1 5
<210> 107
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3高-[抗CD3]_H1.30_L1.47_scFv vlCDR3
<400> 107
Ala Leu Trp Tyr Ser Asn His Trp Val
1 5
<210> 108
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3高-[抗CD3]_H1.30_L1.47_scFv接头
<400> 108
Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly
1 5 10 15
Lys Pro Gly Ser
20
<210> 109
<211> 254
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> CD3高-Int编号1-[抗CD3]_H1.32_L1.47_scFv scFv（VHVL）
<400> 109
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr
20 25 30
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp
50 55 60
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
65 70 75 80
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
85 90 95
Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro
115 120 125
Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly
130 135 140
Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly
145 150 155 160
Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr
165 170 175
Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg
180 185 190
Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg
195 200 205
Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly
210 215 220
Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser
225 230 235 240
Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
245 250
<210> 110
<211> 254
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> CD3高-Int编号1-[抗CD3]_H1.32_L1.47_scFv scFv（VLVH）
<400> 110
Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly
1 5 10 15
Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser
20 25 30
Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly
35 40 45
Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe
50 55 60
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala
65 70 75 80
Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn
85 90 95
His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Lys Pro
100 105 110
Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly
115 120 125
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
130 135 140
Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr
145 150 155 160
Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
165 170 175
Val Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala
180 185 190
Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
195 200 205
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
210 215 220
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp
225 230 235 240
Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
245 250
<210> 111
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> CD3高-Int编号1-[抗CD3]_H1.32_L1.47_scFv可变重链（vh）结构域
<400> 111
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr
20 25 30
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp
50 55 60
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
65 70 75 80
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
85 90 95
Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 125
<210> 112
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3高-Int编号1-[抗CD3]_H1.32_L1.47_scFv vhCDR1
<400> 112
Thr Tyr Ala Met Asn
1 5
<210> 113
<211> 19
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3高-Int编号1-[抗CD3]_H1.32_L1.47_scFv vhCDR2
<400> 113
Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser
1 5 10 15
Val Lys Gly
<210> 114
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3高-Int编号1-[抗CD3]_H1.32_L1.47_scFv vhCDR3
<400> 114
His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe Ala Tyr
1 5 10
<210> 115
<211> 109
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> CD3高-Int编号1-[抗CD3]_H1.32_L1.47_scFv可变轻链（vl）结构域
<400> 115
Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly
1 5 10 15
Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser
20 25 30
Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly
35 40 45
Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe
50 55 60
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala
65 70 75 80
Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn
85 90 95
His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
100 105
<210> 116
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3高-Int编号1-[抗CD3]_H1.32_L1.47_scFv vlCDR1
<400> 116
Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn
1 5 10
<210> 117
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3高-Int编号1-[抗CD3]_H1.32_L1.47_scFv vlCDR2
<400> 117
Gly Thr Asn Lys Arg Ala Pro
1 5
<210> 118
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3高-Int编号1-[抗CD3]_H1.32_L1.47_scFv vlCDR3
<400> 118
Ala Leu Trp Tyr Ser Asn His Trp Val
1 5
<210> 119
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3高-Int编号1-[抗CD3]_H1.32_L1.47_scFv接头
<400> 119
Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly
1 5 10 15
Lys Pro Gly Ser
20
<210> 120
<211> 254
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> CD3高-Int编号2-[抗CD3]_H1.89_L1.47_scFv scFv（VHVL）
<400> 120
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr
20 25 30
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp
50 55 60
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
65 70 75 80
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
85 90 95
Tyr Cys Val Arg His Gly Asn Phe Gly Asp Glu Tyr Val Ser Trp Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro
115 120 125
Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly
130 135 140
Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly
145 150 155 160
Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr
165 170 175
Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg
180 185 190
Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg
195 200 205
Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly
210 215 220
Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser
225 230 235 240
Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
245 250
<210> 121
<211> 254
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> CD3高-Int编号2-[抗CD3]_H1.89_L1.47_scFv scFv（VLVH）
<400> 121
Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly
1 5 10 15
Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser
20 25 30
Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly
35 40 45
Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe
50 55 60
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala
65 70 75 80
Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn
85 90 95
His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Lys Pro
100 105 110
Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly
115 120 125
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
130 135 140
Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr
145 150 155 160
Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
165 170 175
Val Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
180 185 190
Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
195 200 205
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
210 215 220
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asp Glu Tyr Val Ser Trp
225 230 235 240
Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
245 250
<210> 122
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> CD3高-Int编号2-[抗CD3]_H1.89_L1.47_scFv可变重链（vh）结构域
<400> 122
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr
20 25 30
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp
50 55 60
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
65 70 75 80
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
85 90 95
Tyr Cys Val Arg His Gly Asn Phe Gly Asp Glu Tyr Val Ser Trp Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 125
<210> 123
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3高-Int编号2-[抗CD3]_H1.89_L1.47_scFv vhCDR1
<400> 123
Thr Tyr Ala Met Asn
1 5
<210> 124
<211> 19
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3高-Int编号2-[抗CD3]_H1.89_L1.47_scFv vhCDR2
<400> 124
Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser
1 5 10 15
Val Lys Gly
<210> 125
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3高-Int编号2-[抗CD3]_H1.89_L1.47_scFv vhCDR3
<400> 125
His Gly Asn Phe Gly Asp Glu Tyr Val Ser Trp Phe Ala Tyr
1 5 10
<210> 126
<211> 109
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> CD3高-Int编号2-[抗CD3]_H1.89_L1.47_scFv可变轻链（vl）结构域
<400> 126
Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly
1 5 10 15
Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser
20 25 30
Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly
35 40 45
Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe
50 55 60
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala
65 70 75 80
Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn
85 90 95
His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
100 105
<210> 127
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3高-Int编号2-[抗CD3]_H1.89_L1.47_scFv vlCDR1
<400> 127
Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn
1 5 10
<210> 128
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3高-Int编号2-[抗CD3]_H1.89_L1.47_scFv vlCDR2
<400> 128
Gly Thr Asn Lys Arg Ala Pro
1 5
<210> 129
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3高-Int编号2-[抗CD3]_H1.89_L1.47_scFv vlCDR3
<400> 129
Ala Leu Trp Tyr Ser Asn His Trp Val
1 5
<210> 130
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3高-Int编号2-[抗CD3]_H1.89_L1.47_scFv接头
<400> 130
Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly
1 5 10 15
Lys Pro Gly Ser
20
<210> 131
<211> 254
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> CD3高-Int编号3-[抗CD3]_H1.90_L1.47_scFv scFv（VHVL）
<400> 131
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr
20 25 30
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp
50 55 60
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
65 70 75 80
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
85 90 95
Tyr Cys Val Arg His Gly Asn Phe Gly Asp Pro Tyr Val Ser Trp Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro
115 120 125
Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly
130 135 140
Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly
145 150 155 160
Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr
165 170 175
Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg
180 185 190
Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg
195 200 205
Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly
210 215 220
Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser
225 230 235 240
Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
245 250
<210> 132
<211> 254
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> CD3高-Int编号3-[抗CD3]_H1.90_L1.47_scFv scFv（VLVH）
<400> 132
Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly
1 5 10 15
Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser
20 25 30
Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly
35 40 45
Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe
50 55 60
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala
65 70 75 80
Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn
85 90 95
His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Lys Pro
100 105 110
Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly
115 120 125
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
130 135 140
Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr
145 150 155 160
Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
165 170 175
Val Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
180 185 190
Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
195 200 205
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
210 215 220
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asp Pro Tyr Val Ser Trp
225 230 235 240
Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
245 250
<210> 133
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> CD3高-Int编号3-[抗CD3]_H1.90_L1.47_scFv可变重链（vh）结构域
<400> 133
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr
20 25 30
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp
50 55 60
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
65 70 75 80
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
85 90 95
Tyr Cys Val Arg His Gly Asn Phe Gly Asp Pro Tyr Val Ser Trp Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 125
<210> 134
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3高-Int编号3-[抗CD3]_H1.90_L1.47_scFv vhCDR1
<400> 134
Thr Tyr Ala Met Asn
1 5
<210> 135
<211> 19
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3高-Int编号3-[抗CD3]_H1.90_L1.47_scFv vhCDR2
<400> 135
Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser
1 5 10 15
Val Lys Gly
<210> 136
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3高-Int编号3-[抗CD3]_H1.90_L1.47_scFv vhCDR3
<400> 136
His Gly Asn Phe Gly Asp Pro Tyr Val Ser Trp Phe Ala Tyr
1 5 10
<210> 137
<211> 109
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> CD3高-Int编号3-[抗CD3]_H1.90_L1.47_scFv可变轻链（vl）结构域
<400> 137
Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly
1 5 10 15
Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser
20 25 30
Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly
35 40 45
Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe
50 55 60
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala
65 70 75 80
Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn
85 90 95
His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
100 105
<210> 138
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3高-Int编号3-[抗CD3]_H1.90_L1.47_scFv vlCDR1
<400> 138
Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn
1 5 10
<210> 139
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3高-Int编号3-[抗CD3]_H1.90_L1.47_scFv vlCDR2
<400> 139
Gly Thr Asn Lys Arg Ala Pro
1 5
<210> 140
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3高-Int编号3-[抗CD3]_H1.90_L1.47_scFv vlCDR3
<400> 140
Ala Leu Trp Tyr Ser Asn His Trp Val
1 5
<210> 141
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3高-Int编号3-[抗CD3]_H1.90_L1.47_scFv接头
<400> 141
Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly
1 5 10 15
Lys Pro Gly Ser
20
<210> 142
<211> 254
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> CD3-中间体-[抗CD3]_H1.33_L1.47_scFv scFv（VHVL）
<400> 142
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr
20 25 30
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp
50 55 60
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
65 70 75 80
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
85 90 95
Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe
100 105 110
Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro
115 120 125
Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly
130 135 140
Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly
145 150 155 160
Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr
165 170 175
Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg
180 185 190
Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg
195 200 205
Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly
210 215 220
Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser
225 230 235 240
Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
245 250
<210> 143
<211> 254
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> CD3-中间体-[抗CD3]_H1.33_L1.47_scFv scFv（VLVH）
<400> 143
Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly
1 5 10 15
Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser
20 25 30
Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly
35 40 45
Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe
50 55 60
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala
65 70 75 80
Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn
85 90 95
His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Lys Pro
100 105 110
Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly
115 120 125
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
130 135 140
Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr
145 150 155 160
Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
165 170 175
Val Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
180 185 190
Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
195 200 205
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
210 215 220
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp
225 230 235 240
Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
245 250
<210> 144
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> CD3-中间体-[抗CD3]_H1.33_L1.47_scFv可变重链（vh）结构域
<400> 144
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr
20 25 30
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp
50 55 60
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
65 70 75 80
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
85 90 95
Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe
100 105 110
Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 125
<210> 145
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3-中间体-[抗CD3]_H1.33_L1.47_scFv vhCDR1
<400> 145
Thr Tyr Ala Met Asn
1 5
<210> 146
<211> 19
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3-中间体-[抗CD3]_H1.33_L1.47_scFv vhCDR2
<400> 146
Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser
1 5 10 15
Val Lys Gly
<210> 147
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3-中间体-[抗CD3]_H1.33_L1.47_scFv vhCDR3
<400> 147
His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe Asp Tyr
1 5 10
<210> 148
<211> 109
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> CD3-中间体-[抗CD3]_H1.33_L1.47_scFv可变轻链（vl）结构域
<400> 148
Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly
1 5 10 15
Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser
20 25 30
Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly
35 40 45
Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe
50 55 60
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala
65 70 75 80
Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn
85 90 95
His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
100 105
<210> 149
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3-中间体-[抗CD3]_H1.33_L1.47_scFv vlCDR1
<400> 149
Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn
1 5 10
<210> 150
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3-中间体-[抗CD3]_H1.33_L1.47_scFv vlCDR2
<400> 150
Gly Thr Asn Lys Arg Ala Pro
1 5
<210> 151
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3-中间体-[抗CD3]_H1.33_L1.47_scFv vlCDR3
<400> 151
Ala Leu Trp Tyr Ser Asn His Trp Val
1 5
<210> 152
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3-中间体-[抗CD3]_H1.33_L1.47_scFv接头
<400> 152
Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly
1 5 10 15
Lys Pro Gly Ser
20
<210> 153
<211> 254
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> CD3低-[抗CD3]_H1.31_L1.47_scFv scFv（VHVL）
<400> 153
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr
20 25 30
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp
50 55 60
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
65 70 75 80
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
85 90 95
Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro
115 120 125
Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly
130 135 140
Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly
145 150 155 160
Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr
165 170 175
Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg
180 185 190
Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg
195 200 205
Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly
210 215 220
Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser
225 230 235 240
Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
245 250
<210> 154
<211> 254
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> CD3低-[抗CD3]_H1.31_L1.47_scFv scFv（VLVH）
<400> 154
Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly
1 5 10 15
Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser
20 25 30
Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly
35 40 45
Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe
50 55 60
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala
65 70 75 80
Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn
85 90 95
His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Lys Pro
100 105 110
Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly
115 120 125
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
130 135 140
Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr
145 150 155 160
Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
165 170 175
Val Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
180 185 190
Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
195 200 205
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
210 215 220
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp
225 230 235 240
Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
245 250
<210> 155
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> CD3低-[抗CD3]_H1.31_L1.47_scFv可变重链（vh）结构域
<400> 155
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr
20 25 30
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp
50 55 60
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
65 70 75 80
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
85 90 95
Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 125
<210> 156
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3低-[抗CD3]_H1.31_L1.47_scFv vhCDR1
<400> 156
Thr Tyr Ala Met Ser
1 5
<210> 157
<211> 19
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3低-[抗CD3]_H1.31_L1.47_scFv vhCDR2
<400> 157
Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser
1 5 10 15
Val Lys Gly
<210> 158
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3低-[抗CD3]_H1.31_L1.47_scFv vhCDR3
<400> 158
His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe Ala Tyr
1 5 10
<210> 159
<211> 109
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> CD3低-[抗CD3]_H1.31_L1.47_scFv可变轻链（vl）结构域
<400> 159
Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly
1 5 10 15
Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser
20 25 30
Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly
35 40 45
Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe
50 55 60
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala
65 70 75 80
Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn
85 90 95
His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
100 105
<210> 160
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3低-[抗CD3]_H1.31_L1.47_scFv vlCDR1
<400> 160
Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn
1 5 10
<210> 161
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3低-[抗CD3]_H1.31_L1.47_scFv vlCDR2
<400> 161
Gly Thr Asn Lys Arg Ala Pro
1 5
<210> 162
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3低-[抗CD3]_H1.31_L1.47_scFv vlCDR3
<400> 162
Ala Leu Trp Tyr Ser Asn His Trp Val
1 5
<210> 163
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> CD3低-[抗CD3]_H1.31_L1.47_scFv接头
<400> 163
Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly
1 5 10 15
Lys Pro Gly Ser
20
<210> 164
<211> 580
<212> PRT
<213> 智人（Homo sapiens）
<220>
<223> 人GPC3序列sp|P51654
<400> 164
Met Ala Gly Thr Val Arg Thr Ala Cys Leu Val Val Ala Met Leu Leu
1 5 10 15
Ser Leu Asp Phe Pro Gly Gln Ala Gln Pro Pro Pro Pro Pro Pro Asp
20 25 30
Ala Thr Cys His Gln Val Arg Ser Phe Phe Gln Arg Leu Gln Pro Gly
35 40 45
Leu Lys Trp Val Pro Glu Thr Pro Val Pro Gly Ser Asp Leu Gln Val
50 55 60
Cys Leu Pro Lys Gly Pro Thr Cys Cys Ser Arg Lys Met Glu Glu Lys
65 70 75 80
Tyr Gln Leu Thr Ala Arg Leu Asn Met Glu Gln Leu Leu Gln Ser Ala
85 90 95
Ser Met Glu Leu Lys Phe Leu Ile Ile Gln Asn Ala Ala Val Phe Gln
100 105 110
Glu Ala Phe Glu Ile Val Val Arg His Ala Lys Asn Tyr Thr Asn Ala
115 120 125
Met Phe Lys Asn Asn Tyr Pro Ser Leu Thr Pro Gln Ala Phe Glu Phe
130 135 140
Val Gly Glu Phe Phe Thr Asp Val Ser Leu Tyr Ile Leu Gly Ser Asp
145 150 155 160
Ile Asn Val Asp Asp Met Val Asn Glu Leu Phe Asp Ser Leu Phe Pro
165 170 175
Val Ile Tyr Thr Gln Leu Met Asn Pro Gly Leu Pro Asp Ser Ala Leu
180 185 190
Asp Ile Asn Glu Cys Leu Arg Gly Ala Arg Arg Asp Leu Lys Val Phe
195 200 205
Gly Asn Phe Pro Lys Leu Ile Met Thr Gln Val Ser Lys Ser Leu Gln
210 215 220
Val Thr Arg Ile Phe Leu Gln Ala Leu Asn Leu Gly Ile Glu Val Ile
225 230 235 240
Asn Thr Thr Asp His Leu Lys Phe Ser Lys Asp Cys Gly Arg Met Leu
245 250 255
Thr Arg Met Trp Tyr Cys Ser Tyr Cys Gln Gly Leu Met Met Val Lys
260 265 270
Pro Cys Gly Gly Tyr Cys Asn Val Val Met Gln Gly Cys Met Ala Gly
275 280 285
Val Val Glu Ile Asp Lys Tyr Trp Arg Glu Tyr Ile Leu Ser Leu Glu
290 295 300
Glu Leu Val Asn Gly Met Tyr Arg Ile Tyr Asp Met Glu Asn Val Leu
305 310 315 320
Leu Gly Leu Phe Ser Thr Ile His Asp Ser Ile Gln Tyr Val Gln Lys
325 330 335
Asn Ala Gly Lys Leu Thr Thr Thr Ile Gly Lys Leu Cys Ala His Ser
340 345 350
Gln Gln Arg Gln Tyr Arg Ser Ala Tyr Tyr Pro Glu Asp Leu Phe Ile
355 360 365
Asp Lys Lys Val Leu Lys Val Ala His Val Glu His Glu Glu Thr Leu
370 375 380
Ser Ser Arg Arg Arg Glu Leu Ile Gln Lys Leu Lys Ser Phe Ile Ser
385 390 395 400
Phe Tyr Ser Ala Leu Pro Gly Tyr Ile Cys Ser His Ser Pro Val Ala
405 410 415
Glu Asn Asp Thr Leu Cys Trp Asn Gly Gln Glu Leu Val Glu Arg Tyr
420 425 430
Ser Gln Lys Ala Ala Arg Asn Gly Met Lys Asn Gln Phe Asn Leu His
435 440 445
Glu Leu Lys Met Lys Gly Pro Glu Pro Val Val Ser Gln Ile Ile Asp
450 455 460
Lys Leu Lys His Ile Asn Gln Leu Leu Arg Thr Met Ser Met Pro Lys
465 470 475 480
Gly Arg Val Leu Asp Lys Asn Leu Asp Glu Glu Gly Phe Glu Ser Gly
485 490 495
Asp Cys Gly Asp Asp Glu Asp Glu Cys Ile Gly Gly Ser Gly Asp Gly
500 505 510
Met Ile Lys Val Lys Asn Gln Leu Arg Phe Leu Ala Glu Leu Ala Tyr
515 520 525
Asp Leu Asp Val Asp Asp Ala Pro Gly Asn Ser Gln Gln Ala Thr Pro
530 535 540
Lys Asp Asn Glu Ile Ser Thr Phe His Asn Leu Gly Asn Val His Ser
545 550 555 560
Pro Leu Lys Leu Leu Thr Ser Met Ala Ile Ser Val Val Cys Phe Phe
565 570 575
Phe Leu Val His
580
<210> 165
<211> 334
<212> PRT
<213> 智人
<220>
<223> 人GPC3序列，α亚基sp|P51654|25-358
<400> 165
Gln Pro Pro Pro Pro Pro Pro Asp Ala Thr Cys His Gln Val Arg Ser
1 5 10 15
Phe Phe Gln Arg Leu Gln Pro Gly Leu Lys Trp Val Pro Glu Thr Pro
20 25 30
Val Pro Gly Ser Asp Leu Gln Val Cys Leu Pro Lys Gly Pro Thr Cys
35 40 45
Cys Ser Arg Lys Met Glu Glu Lys Tyr Gln Leu Thr Ala Arg Leu Asn
50 55 60
Met Glu Gln Leu Leu Gln Ser Ala Ser Met Glu Leu Lys Phe Leu Ile
65 70 75 80
Ile Gln Asn Ala Ala Val Phe Gln Glu Ala Phe Glu Ile Val Val Arg
85 90 95
His Ala Lys Asn Tyr Thr Asn Ala Met Phe Lys Asn Asn Tyr Pro Ser
100 105 110
Leu Thr Pro Gln Ala Phe Glu Phe Val Gly Glu Phe Phe Thr Asp Val
115 120 125
Ser Leu Tyr Ile Leu Gly Ser Asp Ile Asn Val Asp Asp Met Val Asn
130 135 140
Glu Leu Phe Asp Ser Leu Phe Pro Val Ile Tyr Thr Gln Leu Met Asn
145 150 155 160
Pro Gly Leu Pro Asp Ser Ala Leu Asp Ile Asn Glu Cys Leu Arg Gly
165 170 175
Ala Arg Arg Asp Leu Lys Val Phe Gly Asn Phe Pro Lys Leu Ile Met
180 185 190
Thr Gln Val Ser Lys Ser Leu Gln Val Thr Arg Ile Phe Leu Gln Ala
195 200 205
Leu Asn Leu Gly Ile Glu Val Ile Asn Thr Thr Asp His Leu Lys Phe
210 215 220
Ser Lys Asp Cys Gly Arg Met Leu Thr Arg Met Trp Tyr Cys Ser Tyr
225 230 235 240
Cys Gln Gly Leu Met Met Val Lys Pro Cys Gly Gly Tyr Cys Asn Val
245 250 255
Val Met Gln Gly Cys Met Ala Gly Val Val Glu Ile Asp Lys Tyr Trp
260 265 270
Arg Glu Tyr Ile Leu Ser Leu Glu Glu Leu Val Asn Gly Met Tyr Arg
275 280 285
Ile Tyr Asp Met Glu Asn Val Leu Leu Gly Leu Phe Ser Thr Ile His
290 295 300
Asp Ser Ile Gln Tyr Val Gln Lys Asn Ala Gly Lys Leu Thr Thr Thr
305 310 315 320
Ile Gly Lys Leu Cys Ala His Ser Gln Gln Arg Gln Tyr Arg
325 330
<210> 166
<211> 196
<212> PRT
<213> 智人
<220>
<223> 人GPC3序列，β亚基sp|P51654|359-554
<400> 166
Ser Ala Tyr Tyr Pro Glu Asp Leu Phe Ile Asp Lys Lys Val Leu Lys
1 5 10 15
Val Ala His Val Glu His Glu Glu Thr Leu Ser Ser Arg Arg Arg Glu
20 25 30
Leu Ile Gln Lys Leu Lys Ser Phe Ile Ser Phe Tyr Ser Ala Leu Pro
35 40 45
Gly Tyr Ile Cys Ser His Ser Pro Val Ala Glu Asn Asp Thr Leu Cys
50 55 60
Trp Asn Gly Gln Glu Leu Val Glu Arg Tyr Ser Gln Lys Ala Ala Arg
65 70 75 80
Asn Gly Met Lys Asn Gln Phe Asn Leu His Glu Leu Lys Met Lys Gly
85 90 95
Pro Glu Pro Val Val Ser Gln Ile Ile Asp Lys Leu Lys His Ile Asn
100 105 110
Gln Leu Leu Arg Thr Met Ser Met Pro Lys Gly Arg Val Leu Asp Lys
115 120 125
Asn Leu Asp Glu Glu Gly Phe Glu Ser Gly Asp Cys Gly Asp Asp Glu
130 135 140
Asp Glu Cys Ile Gly Gly Ser Gly Asp Gly Met Ile Lys Val Lys Asn
145 150 155 160
Gln Leu Arg Phe Leu Ala Glu Leu Ala Tyr Asp Leu Asp Val Asp Asp
165 170 175
Ala Pro Gly Asn Ser Gln Gln Ala Thr Pro Lys Asp Asn Glu Ile Ser
180 185 190
Thr Phe His Asn
195
<210> 167
<211> 580
<212> PRT
<213> 食蟹猕猴（Macaca fascicularis）
<220>
<223> 食蟹猕猴GPC3序列tr|A0A2K5VK50
<400> 167
Met Ala Gly Thr Val Arg Thr Ala Cys Leu Val Val Ala Met Leu Leu
1 5 10 15
Ser Leu Asp Phe Pro Gly Gln Ala Gln Pro Pro Pro Pro Pro Pro Asp
20 25 30
Ala Thr Cys His Gln Val Arg Ser Phe Phe Gln Arg Leu Gln Pro Gly
35 40 45
Leu Lys Trp Val Pro Glu Thr Pro Val Pro Gly Ser Asp Leu Gln Val
50 55 60
Cys Leu Pro Lys Gly Pro Thr Cys Cys Ser Arg Lys Met Glu Glu Lys
65 70 75 80
Tyr Gln Leu Thr Ala Arg Leu Asn Met Glu Gln Leu Leu Gln Ser Ala
85 90 95
Ser Met Glu Leu Lys Phe Leu Ile Ile Gln Asn Ala Ala Val Phe Gln
100 105 110
Glu Ala Phe Glu Ile Val Val Arg His Ala Lys Asn Tyr Thr Asn Ala
115 120 125
Met Phe Lys Asn Asn Tyr Pro Ser Leu Thr Pro Gln Ala Phe Glu Phe
130 135 140
Val Gly Glu Phe Phe Thr Asp Val Ser Leu Tyr Ile Leu Gly Ser Asp
145 150 155 160
Ile Asn Val Asp Asp Met Val Asn Glu Leu Phe Asp Ser Leu Phe Pro
165 170 175
Val Ile Tyr Thr Gln Leu Met Asn Pro Gly Leu Pro Asp Ser Ala Leu
180 185 190
Asp Ile Asn Glu Cys Leu Arg Gly Ala Arg Arg Asp Leu Lys Val Phe
195 200 205
Gly Asn Phe Pro Lys Leu Ile Met Thr Gln Val Ser Lys Ser Leu Gln
210 215 220
Val Thr Arg Ile Phe Leu Gln Ala Leu Asn Leu Gly Ile Glu Val Ile
225 230 235 240
Asn Thr Thr Asp His Leu Lys Phe Ser Lys Asp Cys Gly Arg Met Leu
245 250 255
Thr Arg Met Trp Tyr Cys Ser Tyr Cys Gln Gly Leu Met Met Val Lys
260 265 270
Pro Cys Gly Gly Tyr Cys Asn Val Val Met Gln Gly Cys Met Ala Gly
275 280 285
Val Val Glu Ile Asp Lys Tyr Trp Arg Glu Tyr Ile Leu Ser Leu Glu
290 295 300
Glu Leu Val Asn Gly Met Tyr Arg Ile Tyr Asp Met Glu Asn Val Leu
305 310 315 320
Leu Gly Leu Phe Ser Thr Ile His Asp Ser Ile Gln Tyr Val Gln Lys
325 330 335
Asn Ala Gly Lys Leu Thr Thr Thr Ile Gly Lys Leu Cys Ala His Ser
340 345 350
Gln Gln Arg Gln Tyr Arg Ser Ala Tyr Tyr Pro Glu Asp Leu Phe Ile
355 360 365
Asp Lys Lys Val Leu Lys Val Ala His Val Glu His Glu Glu Thr Leu
370 375 380
Ser Ser Arg Arg Arg Glu Leu Ile Gln Lys Leu Lys Ser Phe Ile Ser
385 390 395 400
Phe Tyr Ser Ala Leu Pro Gly Tyr Ile Cys Ser His Ser Pro Val Ala
405 410 415
Glu Asn Asp Thr Leu Cys Trp Asn Gly Gln Glu Leu Val Glu Arg Tyr
420 425 430
Ser Gln Lys Ala Ala Arg Asn Gly Met Lys Asn Gln Phe Asn Leu His
435 440 445
Glu Leu Lys Met Lys Gly Pro Glu Pro Val Val Ser Gln Ile Ile Asp
450 455 460
Lys Leu Lys His Ile Asn Gln Leu Leu Arg Thr Met Ser Val Pro Lys
465 470 475 480
Gly Arg Val Leu Asp Lys Asn Leu Asp Glu Glu Gly Phe Glu Ser Gly
485 490 495
Asp Cys Gly Asp Asp Glu Asp Glu Cys Ile Gly Gly Ser Gly Asp Gly
500 505 510
Met Met Lys Val Lys Asn Gln Leu Arg Phe Leu Ala Glu Leu Ala Tyr
515 520 525
Asp Leu Asp Val Asp Asp Val Pro Gly Asn Asn Gln Gln Ala Thr Pro
530 535 540
Lys Asp Asn Glu Ile Ser Thr Phe His Asn Leu Gly Asn Val His Ser
545 550 555 560
Pro Leu Lys Leu Leu Thr Ser Met Ala Ile Ser Val Val Cys Phe Phe
565 570 575
Phe Leu Val His
580
<210> 168
<211> 334
<212> PRT
<213> 食蟹猕猴
<220>
<223> 食蟹猕猴GPC3序列，α亚基（预测）
tr|A0A2K5VK50|25-358
<400> 168
Gln Pro Pro Pro Pro Pro Pro Asp Ala Thr Cys His Gln Val Arg Ser
1 5 10 15
Phe Phe Gln Arg Leu Gln Pro Gly Leu Lys Trp Val Pro Glu Thr Pro
20 25 30
Val Pro Gly Ser Asp Leu Gln Val Cys Leu Pro Lys Gly Pro Thr Cys
35 40 45
Cys Ser Arg Lys Met Glu Glu Lys Tyr Gln Leu Thr Ala Arg Leu Asn
50 55 60
Met Glu Gln Leu Leu Gln Ser Ala Ser Met Glu Leu Lys Phe Leu Ile
65 70 75 80
Ile Gln Asn Ala Ala Val Phe Gln Glu Ala Phe Glu Ile Val Val Arg
85 90 95
His Ala Lys Asn Tyr Thr Asn Ala Met Phe Lys Asn Asn Tyr Pro Ser
100 105 110
Leu Thr Pro Gln Ala Phe Glu Phe Val Gly Glu Phe Phe Thr Asp Val
115 120 125
Ser Leu Tyr Ile Leu Gly Ser Asp Ile Asn Val Asp Asp Met Val Asn
130 135 140
Glu Leu Phe Asp Ser Leu Phe Pro Val Ile Tyr Thr Gln Leu Met Asn
145 150 155 160
Pro Gly Leu Pro Asp Ser Ala Leu Asp Ile Asn Glu Cys Leu Arg Gly
165 170 175
Ala Arg Arg Asp Leu Lys Val Phe Gly Asn Phe Pro Lys Leu Ile Met
180 185 190
Thr Gln Val Ser Lys Ser Leu Gln Val Thr Arg Ile Phe Leu Gln Ala
195 200 205
Leu Asn Leu Gly Ile Glu Val Ile Asn Thr Thr Asp His Leu Lys Phe
210 215 220
Ser Lys Asp Cys Gly Arg Met Leu Thr Arg Met Trp Tyr Cys Ser Tyr
225 230 235 240
Cys Gln Gly Leu Met Met Val Lys Pro Cys Gly Gly Tyr Cys Asn Val
245 250 255
Val Met Gln Gly Cys Met Ala Gly Val Val Glu Ile Asp Lys Tyr Trp
260 265 270
Arg Glu Tyr Ile Leu Ser Leu Glu Glu Leu Val Asn Gly Met Tyr Arg
275 280 285
Ile Tyr Asp Met Glu Asn Val Leu Leu Gly Leu Phe Ser Thr Ile His
290 295 300
Asp Ser Ile Gln Tyr Val Gln Lys Asn Ala Gly Lys Leu Thr Thr Thr
305 310 315 320
Ile Gly Lys Leu Cys Ala His Ser Gln Gln Arg Gln Tyr Arg
325 330
<210> 169
<211> 196
<212> PRT
<213> 食蟹猕猴
<220>
<223> 食蟹猕猴GPC3序列，β亚基（预测）
tr|A0A2K5VK50|359-554
<400> 169
Ser Ala Tyr Tyr Pro Glu Asp Leu Phe Ile Asp Lys Lys Val Leu Lys
1 5 10 15
Val Ala His Val Glu His Glu Glu Thr Leu Ser Ser Arg Arg Arg Glu
20 25 30
Leu Ile Gln Lys Leu Lys Ser Phe Ile Ser Phe Tyr Ser Ala Leu Pro
35 40 45
Gly Tyr Ile Cys Ser His Ser Pro Val Ala Glu Asn Asp Thr Leu Cys
50 55 60
Trp Asn Gly Gln Glu Leu Val Glu Arg Tyr Ser Gln Lys Ala Ala Arg
65 70 75 80
Asn Gly Met Lys Asn Gln Phe Asn Leu His Glu Leu Lys Met Lys Gly
85 90 95
Pro Glu Pro Val Val Ser Gln Ile Ile Asp Lys Leu Lys His Ile Asn
100 105 110
Gln Leu Leu Arg Thr Met Ser Val Pro Lys Gly Arg Val Leu Asp Lys
115 120 125
Asn Leu Asp Glu Glu Gly Phe Glu Ser Gly Asp Cys Gly Asp Asp Glu
130 135 140
Asp Glu Cys Ile Gly Gly Ser Gly Asp Gly Met Met Lys Val Lys Asn
145 150 155 160
Gln Leu Arg Phe Leu Ala Glu Leu Ala Tyr Asp Leu Asp Val Asp Asp
165 170 175
Val Pro Gly Asn Asn Gln Gln Ala Thr Pro Lys Asp Asn Glu Ile Ser
180 185 190
Thr Phe His Asn
195
<210> 170
<211> 579
<212> PRT
<213> 小家鼠（Mus musculus）
<220>
<223> 小鼠GPC3序列sp|Q8CFZ4
<400> 170
Met Ala Gly Thr Val Arg Thr Ala Cys Leu Leu Val Ala Met Leu Leu
1 5 10 15
Gly Leu Gly Cys Leu Gly Gln Ala Gln Pro Pro Pro Pro Pro Asp Ala
20 25 30
Thr Cys His Gln Val Arg Ser Phe Phe Gln Arg Leu Gln Pro Gly Leu
35 40 45
Lys Trp Val Pro Glu Thr Pro Val Pro Gly Ser Asp Leu Gln Val Cys
50 55 60
Leu Pro Lys Gly Pro Thr Cys Cys Ser Arg Lys Met Glu Glu Lys Tyr
65 70 75 80
Gln Leu Thr Ala Arg Leu Asn Met Glu Gln Leu Leu Gln Ser Ala Ser
85 90 95
Met Glu Leu Lys Phe Leu Ile Ile Gln Asn Ala Ala Val Phe Gln Glu
100 105 110
Ala Phe Glu Ile Val Val Arg His Ala Lys Asn Tyr Thr Asn Ala Met
115 120 125
Phe Lys Asn Asn Tyr Pro Ser Leu Thr Pro Gln Ala Phe Glu Phe Val
130 135 140
Gly Glu Phe Phe Thr Asp Val Ser Leu Tyr Ile Leu Gly Ser Asp Ile
145 150 155 160
Asn Val Asp Asp Met Val Asn Glu Leu Phe Asp Ser Leu Phe Pro Val
165 170 175
Ile Tyr Thr Gln Met Met Asn Pro Gly Leu Pro Glu Ser Val Leu Asp
180 185 190
Ile Asn Glu Cys Leu Arg Gly Ala Arg Arg Asp Leu Lys Val Phe Gly
195 200 205
Ser Phe Pro Lys Leu Ile Met Thr Gln Val Ser Lys Ser Leu Gln Val
210 215 220
Thr Arg Ile Phe Leu Gln Ala Leu Asn Leu Gly Ile Glu Val Ile Asn
225 230 235 240
Thr Thr Asp His Leu Lys Phe Ser Lys Asp Cys Gly Arg Met Leu Thr
245 250 255
Arg Met Trp Tyr Cys Ser Tyr Cys Gln Gly Leu Met Met Val Lys Pro
260 265 270
Cys Gly Gly Tyr Cys Asn Val Val Met Gln Gly Cys Met Ala Gly Val
275 280 285
Val Glu Ile Asp Lys Tyr Trp Arg Glu Tyr Ile Leu Ser Leu Glu Glu
290 295 300
Leu Val Asn Gly Met Tyr Arg Ile Tyr Asp Met Glu Asn Val Leu Leu
305 310 315 320
Gly Leu Phe Ser Thr Ile His Asp Ser Ile Gln Tyr Val Gln Lys Asn
325 330 335
Gly Gly Lys Leu Thr Thr Thr Ile Gly Lys Leu Cys Ala His Ser Gln
340 345 350
Gln Arg Gln Tyr Arg Ser Ala Tyr Tyr Pro Glu Asp Leu Phe Ile Asp
355 360 365
Lys Lys Ile Leu Lys Val Ala His Val Glu His Glu Glu Thr Leu Ser
370 375 380
Ser Arg Arg Arg Glu Leu Ile Gln Lys Leu Lys Ser Phe Ile Asn Phe
385 390 395 400
Tyr Ser Ala Leu Pro Gly Tyr Ile Cys Ser His Ser Pro Val Ala Glu
405 410 415
Asn Asp Thr Leu Cys Trp Asn Gly Gln Glu Leu Val Glu Arg Tyr Ser
420 425 430
Gln Lys Ala Ala Arg Asn Gly Met Lys Asn Gln Phe Asn Leu His Glu
435 440 445
Leu Lys Met Lys Gly Pro Glu Pro Val Val Ser Gln Ile Ile Asp Lys
450 455 460
Leu Lys His Ile Asn Gln Leu Leu Arg Thr Met Ser Val Pro Lys Gly
465 470 475 480
Lys Val Leu Asp Lys Ser Leu Asp Glu Glu Gly Leu Glu Ser Gly Asp
485 490 495
Cys Gly Asp Asp Glu Asp Glu Cys Ile Gly Ser Ser Gly Asp Gly Met
500 505 510
Val Lys Val Lys Asn Gln Leu Arg Phe Leu Ala Glu Leu Ala Tyr Asp
515 520 525
Leu Asp Val Asp Asp Ala Pro Gly Asn Lys Gln His Gly Asn Gln Lys
530 535 540
Asp Asn Glu Ile Thr Thr Ser His Ser Val Gly Asn Met Pro Ser Pro
545 550 555 560
Leu Lys Ile Leu Ile Ser Val Ala Ile Tyr Val Ala Cys Phe Phe Phe
565 570 575
Leu Val His
<210> 171
<211> 333
<212> PRT
<213> 小家鼠
<220>
<223> 小鼠GPC3序列，α亚基sp|Q8CFZ4|25-357
<400> 171
Gln Pro Pro Pro Pro Pro Asp Ala Thr Cys His Gln Val Arg Ser Phe
1 5 10 15
Phe Gln Arg Leu Gln Pro Gly Leu Lys Trp Val Pro Glu Thr Pro Val
20 25 30
Pro Gly Ser Asp Leu Gln Val Cys Leu Pro Lys Gly Pro Thr Cys Cys
35 40 45
Ser Arg Lys Met Glu Glu Lys Tyr Gln Leu Thr Ala Arg Leu Asn Met
50 55 60
Glu Gln Leu Leu Gln Ser Ala Ser Met Glu Leu Lys Phe Leu Ile Ile
65 70 75 80
Gln Asn Ala Ala Val Phe Gln Glu Ala Phe Glu Ile Val Val Arg His
85 90 95
Ala Lys Asn Tyr Thr Asn Ala Met Phe Lys Asn Asn Tyr Pro Ser Leu
100 105 110
Thr Pro Gln Ala Phe Glu Phe Val Gly Glu Phe Phe Thr Asp Val Ser
115 120 125
Leu Tyr Ile Leu Gly Ser Asp Ile Asn Val Asp Asp Met Val Asn Glu
130 135 140
Leu Phe Asp Ser Leu Phe Pro Val Ile Tyr Thr Gln Met Met Asn Pro
145 150 155 160
Gly Leu Pro Glu Ser Val Leu Asp Ile Asn Glu Cys Leu Arg Gly Ala
165 170 175
Arg Arg Asp Leu Lys Val Phe Gly Ser Phe Pro Lys Leu Ile Met Thr
180 185 190
Gln Val Ser Lys Ser Leu Gln Val Thr Arg Ile Phe Leu Gln Ala Leu
195 200 205
Asn Leu Gly Ile Glu Val Ile Asn Thr Thr Asp His Leu Lys Phe Ser
210 215 220
Lys Asp Cys Gly Arg Met Leu Thr Arg Met Trp Tyr Cys Ser Tyr Cys
225 230 235 240
Gln Gly Leu Met Met Val Lys Pro Cys Gly Gly Tyr Cys Asn Val Val
245 250 255
Met Gln Gly Cys Met Ala Gly Val Val Glu Ile Asp Lys Tyr Trp Arg
260 265 270
Glu Tyr Ile Leu Ser Leu Glu Glu Leu Val Asn Gly Met Tyr Arg Ile
275 280 285
Tyr Asp Met Glu Asn Val Leu Leu Gly Leu Phe Ser Thr Ile His Asp
290 295 300
Ser Ile Gln Tyr Val Gln Lys Asn Gly Gly Lys Leu Thr Thr Thr Ile
305 310 315 320
Gly Lys Leu Cys Ala His Ser Gln Gln Arg Gln Tyr Arg
325 330
<210> 172
<211> 196
<212> PRT
<213> 小家鼠
<220>
<223> 小鼠GPC3序列，β亚基sp|Q8CFZ4|358-553
<400> 172
Ser Ala Tyr Tyr Pro Glu Asp Leu Phe Ile Asp Lys Lys Ile Leu Lys
1 5 10 15
Val Ala His Val Glu His Glu Glu Thr Leu Ser Ser Arg Arg Arg Glu
20 25 30
Leu Ile Gln Lys Leu Lys Ser Phe Ile Asn Phe Tyr Ser Ala Leu Pro
35 40 45
Gly Tyr Ile Cys Ser His Ser Pro Val Ala Glu Asn Asp Thr Leu Cys
50 55 60
Trp Asn Gly Gln Glu Leu Val Glu Arg Tyr Ser Gln Lys Ala Ala Arg
65 70 75 80
Asn Gly Met Lys Asn Gln Phe Asn Leu His Glu Leu Lys Met Lys Gly
85 90 95
Pro Glu Pro Val Val Ser Gln Ile Ile Asp Lys Leu Lys His Ile Asn
100 105 110
Gln Leu Leu Arg Thr Met Ser Val Pro Lys Gly Lys Val Leu Asp Lys
115 120 125
Ser Leu Asp Glu Glu Gly Leu Glu Ser Gly Asp Cys Gly Asp Asp Glu
130 135 140
Asp Glu Cys Ile Gly Ser Ser Gly Asp Gly Met Val Lys Val Lys Asn
145 150 155 160
Gln Leu Arg Phe Leu Ala Glu Leu Ala Tyr Asp Leu Asp Val Asp Asp
165 170 175
Ala Pro Gly Asn Lys Gln His Gly Asn Gln Lys Asp Asn Glu Ile Thr
180 185 190
Thr Ser His Ser
195
<210> 173
<211> 115
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> GPC3-A[GPC3]_H1可变重链（vh）结构域
<400> 173
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser
115
<210> 174
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_H1 vhCDR1
<400> 174
Asp Tyr Glu Met His
1 5
<210> 175
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_H1 vhCDR2
<400> 175
Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe Gln
1 5 10 15
Gly
<210> 176
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_H1 vhCDR3
<400> 176
Phe Tyr Ser Tyr Thr Tyr
1 5
<210> 177
<211> 112
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> GPC3-A[GPC3]_L1可变轻链（vl）结构域
<400> 177
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 178
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_L1 vlCDR1
<400> 178
Arg Ser Ser Gln Ser Leu Val His Ser Asn Gly Asn Thr Tyr Leu His
1 5 10 15
<210> 179
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_L1 vlCDR2
<400> 179
Lys Val Ser Asn Arg Phe Ser
1 5
<210> 180
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_L1 vlCDR3
<400> 180
Ser Gln Asn Thr His Val Pro Pro Thr
1 5
<210> 181
<211> 115
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> GPC3-A[GPC3]_H1.1可变重链（vh）结构域
<400> 181
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser
115
<210> 182
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_H1.1 vhCDR1
<400> 182
Asp Tyr Glu Met His
1 5
<210> 183
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_H1.1 vhCDR2
<400> 183
Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe Gln
1 5 10 15
Gly
<210> 184
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_H1.1 vhCDR3
<400> 184
Phe Tyr Ser Tyr Thr Tyr
1 5
<210> 185
<211> 115
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> GPC3-A[GPC3]_H1.2可变重链（vh）结构域
<400> 185
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Asn Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser
115
<210> 186
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_H1.2 vhCDR1
<400> 186
Asp Tyr Glu Met His
1 5
<210> 187
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_H1.2 vhCDR2
<400> 187
Ala Leu Asn Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe Gln
1 5 10 15
Gly
<210> 188
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_H1.2 vhCDR3
<400> 188
Phe Tyr Ser Tyr Thr Tyr
1 5
<210> 189
<211> 115
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> GPC3-A[GPC3]_H1.3可变重链（vh）结构域
<400> 189
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Gln Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser
115
<210> 190
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_H1.3 vhCDR1
<400> 190
Asp Tyr Glu Met His
1 5
<210> 191
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_H1.3 vhCDR2
<400> 191
Ala Leu Gln Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe Gln
1 5 10 15
Gly
<210> 192
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_H1.3 vhCDR3
<400> 192
Phe Tyr Ser Tyr Thr Tyr
1 5
<210> 193
<211> 115
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> GPC3-A[GPC3]_H1.4可变重链（vh）结构域
<400> 193
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Ser Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser
115
<210> 194
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_H1.4 vhCDR1
<400> 194
Asp Tyr Glu Met His
1 5
<210> 195
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_H1.4 vhCDR2
<400> 195
Ala Leu Ser Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe Gln
1 5 10 15
Gly
<210> 196
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_H1.4 vhCDR3
<400> 196
Phe Tyr Ser Tyr Thr Tyr
1 5
<210> 197
<211> 115
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> GPC3-A[GPC3]_ L1.1可变轻链（vl）结构域
<400> 197
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser
115
<210> 198
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.1 vlCDR1
<400> 198
Asp Tyr Glu Met His
1 5
<210> 199
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.1 vlCDR2
<400> 199
Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe Gln
1 5 10 15
Gly
<210> 200
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.1 vlCDR3
<400> 200
Phe Tyr Ser Tyr Thr Tyr
1 5
<210> 201
<211> 115
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> GPC3-A[GPC3]_ L1.2可变轻链（vl）结构域
<400> 201
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser
115
<210> 202
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.2 vlCDR1
<400> 202
Asp Tyr Glu Met His
1 5
<210> 203
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.2 vlCDR2
<400> 203
Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe Gln
1 5 10 15
Gly
<210> 204
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.2 vlCDR3
<400> 204
Phe Tyr Ser Tyr Thr Tyr
1 5
<210> 205
<211> 115
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> GPC3-A[GPC3]_ L1.3可变轻链（vl）结构域
<400> 205
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser
115
<210> 206
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.3 vlCDR1
<400> 206
Asp Tyr Glu Met His
1 5
<210> 207
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.3 vlCDR2
<400> 207
Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe Gln
1 5 10 15
Gly
<210> 208
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.3 vlCDR3
<400> 208
Phe Tyr Ser Tyr Thr Tyr
1 5
<210> 209
<211> 115
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> GPC3-A[GPC3]_ L1.4可变轻链（vl）结构域
<400> 209
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser
115
<210> 210
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.4 vlCDR1
<400> 210
Asp Tyr Glu Met His
1 5
<210> 211
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.4 vlCDR2
<400> 211
Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe Gln
1 5 10 15
Gly
<210> 212
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.4 vlCDR3
<400> 212
Phe Tyr Ser Tyr Thr Tyr
1 5
<210> 213
<211> 115
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> GPC3-A[GPC3]_ L1.5可变轻链（vl）结构域
<400> 213
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser
115
<210> 214
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.5 vlCDR1
<400> 214
Asp Tyr Glu Met His
1 5
<210> 215
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.5 vlCDR2
<400> 215
Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe Gln
1 5 10 15
Gly
<210> 216
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.5 vlCDR3
<400> 216
Phe Tyr Ser Tyr Thr Tyr
1 5
<210> 217
<211> 112
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> GPC3-A[GPC3]_ L1.6可变轻链（vl）结构域
<400> 217
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Thr Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 218
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.6 vlCDR1
<400> 218
Arg Ser Ser Gln Ser Leu Val His Ser Asn Thr Asn Thr Tyr Leu His
1 5 10 15
<210> 219
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.6 vlCDR2
<400> 219
Lys Val Ser Asn Arg Phe Ser
1 5
<210> 220
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.6 vlCDR3
<400> 220
Ser Gln Asn Thr His Val Pro Pro Thr
1 5
<210> 221
<211> 115
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> GPC3-A[GPC3]_ L1.7可变轻链（vl）结构域
<400> 221
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser
115
<210> 222
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.7 vlCDR1
<400> 222
Asp Tyr Glu Met His
1 5
<210> 223
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.7 vlCDR2
<400> 223
Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe Gln
1 5 10 15
Gly
<210> 224
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.7 vlCDR3
<400> 224
Phe Tyr Ser Tyr Thr Tyr
1 5
<210> 225
<211> 115
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> GPC3-A[GPC3]_ L1.8可变轻链（vl）结构域
<400> 225
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser
115
<210> 226
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.8 vlCDR1
<400> 226
Asp Tyr Glu Met His
1 5
<210> 227
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.8 vlCDR2
<400> 227
Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe Gln
1 5 10 15
Gly
<210> 228
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.8 vlCDR3
<400> 228
Phe Tyr Ser Tyr Thr Tyr
1 5
<210> 229
<211> 115
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> GPC3-A[GPC3]_ L1.9可变轻链（vl）结构域
<400> 229
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser
115
<210> 230
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.9 vlCDR1
<400> 230
Asp Tyr Glu Met His
1 5
<210> 231
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.9 vlCDR2
<400> 231
Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe Gln
1 5 10 15
Gly
<210> 232
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.9 vlCDR3
<400> 232
Phe Tyr Ser Tyr Thr Tyr
1 5
<210> 233
<211> 115
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> GPC3-A[GPC3]_ L1.10可变轻链（vl）结构域
<400> 233
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser
115
<210> 234
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.10 vlCDR1
<400> 234
Asp Tyr Glu Met His
1 5
<210> 235
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.10 vlCDR2
<400> 235
Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe Gln
1 5 10 15
Gly
<210> 236
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.10 vlCDR3
<400> 236
Phe Tyr Ser Tyr Thr Tyr
1 5
<210> 237
<211> 112
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> GPC3-A[GPC3]_ L1.16可变轻链（vl）结构域
<400> 237
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Ser Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Ser
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 238
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.16 vlCDR1
<400> 238
Arg Ser Ser Gln Ser Leu Val His Ser Ser Gly Asn Thr Tyr Leu His
1 5 10 15
<210> 239
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.16 vlCDR2
<400> 239
Lys Val Ser Asn Arg Phe Ser
1 5
<210> 240
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.16 vlCDR3
<400> 240
Ser Gln Ser Thr His Val Pro Pro Thr
1 5
<210> 241
<211> 112
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> GPC3-A[GPC3]_ L1.23可变轻链（vl）结构域
<400> 241
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Gly Asn Thr Trp Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 242
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.23 vlCDR1
<400> 242
Arg Ser Ser Gln Ser Leu Val His Ser Asn Gly Asn Thr Trp Leu His
1 5 10 15
<210> 243
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.23 vlCDR2
<400> 243
Lys Val Ser Asn Arg Phe Ser
1 5
<210> 244
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.23 vlCDR3
<400> 244
Ser Gln Asn Thr His Val Pro Pro Thr
1 5
<210> 245
<211> 112
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> GPC3-A[GPC3]_ L1.29可变轻链（vl）结构域
<400> 245
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Gln Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 246
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.29 vlCDR1
<400> 246
Arg Ser Ser Gln Ser Leu Val His Ser Asn Gly Asn Thr Tyr Leu His
1 5 10 15
<210> 247
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.29 vlCDR2
<400> 247
Gln Val Ser Asn Arg Phe Ser
1 5
<210> 248
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.29 vlCDR3
<400> 248
Ser Gln Asn Thr His Val Pro Pro Thr
1 5
<210> 249
<211> 112
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> GPC3-A[GPC3]_ L1.31可变轻链（vl）结构域
<400> 249
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Tyr Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 250
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.31 vlCDR1
<400> 250
Arg Ser Ser Gln Ser Leu Val His Ser Asn Gly Asn Thr Tyr Leu His
1 5 10 15
<210> 251
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.31 vlCDR2
<400> 251
Tyr Val Ser Asn Arg Phe Ser
1 5
<210> 252
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.31 vlCDR3
<400> 252
Ser Gln Asn Thr His Val Pro Pro Thr
1 5
<210> 253
<211> 112
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> GPC3-A[GPC3]_ L1.65可变轻链（vl）结构域
<400> 253
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Tyr Gly Asn Thr Trp Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 254
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.65 vlCDR1
<400> 254
Arg Ser Ser Gln Ser Leu Val His Ser Tyr Gly Asn Thr Trp Leu His
1 5 10 15
<210> 255
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.65 vlCDR2
<400> 255
Lys Val Ser Asn Arg Phe Ser
1 5
<210> 256
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.65 vlCDR3
<400> 256
Ser Gln Asn Thr His Val Pro Pro Thr
1 5
<210> 257
<211> 112
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> GPC3-A[GPC3]_ L1.66可变轻链（vl）结构域
<400> 257
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Ala Asn Thr Trp Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 258
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.66 vlCDR1
<400> 258
Arg Ser Ser Gln Ser Leu Val His Ser Asn Ala Asn Thr Trp Leu His
1 5 10 15
<210> 259
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.66 vlCDR2
<400> 259
Lys Val Ser Asn Arg Phe Ser
1 5
<210> 260
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.66 vlCDR3
<400> 260
Ser Gln Asn Thr His Val Pro Pro Thr
1 5
<210> 261
<211> 112
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> GPC3-A[GPC3]_ L1.67可变轻链（vl）结构域
<400> 261
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Lys Asn Thr Trp Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 262
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.67 vlCDR1
<400> 262
Arg Ser Ser Gln Ser Leu Val His Ser Asn Lys Asn Thr Trp Leu His
1 5 10 15
<210> 263
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.67 vlCDR2
<400> 263
Lys Val Ser Asn Arg Phe Ser
1 5
<210> 264
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.67 vlCDR3
<400> 264
Ser Gln Asn Thr His Val Pro Pro Thr
1 5
<210> 265
<211> 112
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> GPC3-A[GPC3]_ L1.68可变轻链（vl）结构域
<400> 265
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Tyr Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Gln Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 266
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.68 vlCDR1
<400> 266
Arg Ser Ser Gln Ser Leu Val His Ser Tyr Gly Asn Thr Tyr Leu His
1 5 10 15
<210> 267
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.68 vlCDR2
<400> 267
Gln Val Ser Asn Arg Phe Ser
1 5
<210> 268
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.68 vlCDR3
<400> 268
Ser Gln Asn Thr His Val Pro Pro Thr
1 5
<210> 269
<211> 112
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> GPC3-A[GPC3]_ L1.69可变轻链（vl）结构域
<400> 269
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Ala Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Gln Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 270
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.69 vlCDR1
<400> 270
Arg Ser Ser Gln Ser Leu Val His Ser Asn Ala Asn Thr Tyr Leu His
1 5 10 15
<210> 271
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.69 vlCDR2
<400> 271
Gln Val Ser Asn Arg Phe Ser
1 5
<210> 272
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.69 vlCDR3
<400> 272
Ser Gln Asn Thr His Val Pro Pro Thr
1 5
<210> 273
<211> 112
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> GPC3-A[GPC3]_ L1.70可变轻链（vl）结构域
<400> 273
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Lys Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Gln Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 274
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.70 vlCDR1
<400> 274
Arg Ser Ser Gln Ser Leu Val His Ser Asn Lys Asn Thr Tyr Leu His
1 5 10 15
<210> 275
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.70 vlCDR2
<400> 275
Gln Val Ser Asn Arg Phe Ser
1 5
<210> 276
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.70 vlCDR3
<400> 276
Ser Gln Asn Thr His Val Pro Pro Thr
1 5
<210> 277
<211> 112
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> GPC3-A[GPC3]_ L1.71可变轻链（vl）结构域
<400> 277
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Tyr Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Tyr Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 278
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.71 vlCDR1
<400> 278
Arg Ser Ser Gln Ser Leu Val His Ser Tyr Gly Asn Thr Tyr Leu His
1 5 10 15
<210> 279
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.71 vlCDR2
<400> 279
Tyr Val Ser Asn Arg Phe Ser
1 5
<210> 280
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.71 vlCDR3
<400> 280
Ser Gln Asn Thr His Val Pro Pro Thr
1 5
<210> 281
<211> 112
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> GPC3-A[GPC3]_ L1.72可变轻链（vl）结构域
<400> 281
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Ala Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Tyr Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 282
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.72 vlCDR1
<400> 282
Arg Ser Ser Gln Ser Leu Val His Ser Asn Ala Asn Thr Tyr Leu His
1 5 10 15
<210> 283
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.72 vlCDR2
<400> 283
Tyr Val Ser Asn Arg Phe Ser
1 5
<210> 284
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.72 vlCDR3
<400> 284
Ser Gln Asn Thr His Val Pro Pro Thr
1 5
<210> 285
<211> 112
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> GPC3-A[GPC3]_ L1.73可变轻链（vl）结构域
<400> 285
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Lys Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Tyr Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 286
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.73 vlCDR1
<400> 286
Arg Ser Ser Gln Ser Leu Val His Ser Asn Lys Asn Thr Tyr Leu His
1 5 10 15
<210> 287
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.73 vlCDR2
<400> 287
Tyr Val Ser Asn Arg Phe Ser
1 5
<210> 288
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成肽
<220>
<223> GPC3-A[GPC3]_ L1.73 vlCDR3
<400> 288
Ser Gln Asn Thr His Val Pro Pro Thr
1 5
<210> 289
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP21969链1-GPC3-A_H1_[GPC3]_IgG1_PVA_/S267K重链
<400> 289
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
405 410 415
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 290
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP21969链2-GPC3-A[GPC3]_L1轻链
<400> 290
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 291
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP23060链1-GPC3-A_[GPC3]_H1.1_IgG1_PVA_/S267K重链
<400> 291
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
405 410 415
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 292
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP23060链2-GPC3-A_[GPC3]_L1轻链
<400> 292
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 293
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP23061链1-GPC3-A_[GPC3]_H1.2_IgG1_PVA_/S267K重链
<400> 293
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Asn Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
405 410 415
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 294
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP23061链2-GPC3-A_[GPC3]_L1轻链
<400> 294
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 295
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP23062链1-GPC3-A_[GPC3]_H1.3_IgG1_PVA_/S267K重链
<400> 295
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Gln Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
405 410 415
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 296
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP23062链2-GPC3-A_[GPC3]_L1轻链
<400> 296
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 297
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP23063链1-GPC3-A_[GPC3]_H1.4_IgG1_PVA_/S267K重链
<400> 297
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Ser Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
405 410 415
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 298
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP23063链2-GPC3-A_[GPC3]_L1轻链
<400> 298
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 299
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP23064链1-GPC3-A_[GPC3]_H1_IgG1_PVA_/S267K重链
<400> 299
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
405 410 415
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 300
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP23064链2-GPC3-A_[GPC3]_L1.1轻链
<400> 300
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Gln Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 301
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP23065链1-GPC3-A_[GPC3]_H1_IgG1_PVA_/S267K重链
<400> 301
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
405 410 415
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 302
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP23065链2-GPC3-A_[GPC3]_L1.2轻链
<400> 302
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Tyr Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 303
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP23066链1-GPC3-A_[GPC3]_H1_IgG1_PVA_/S267K重链
<400> 303
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
405 410 415
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 304
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP23066链2-GPC3-A_[GPC3]_L1.3轻链
<400> 304
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Ser Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 305
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP23067链1-GPC3-A_[GPC3]_H1_IgG1_PVA_/S267K重链
<400> 305
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
405 410 415
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 306
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP23067链2-GPC3-A_[GPC3]_L1.4轻链
<400> 306
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
His Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 307
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP23068链1-GPC3-A_[GPC3]_H1_IgG1_PVA_/S267K重链
<400> 307
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
405 410 415
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 308
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP23068链2-GPC3-A_[GPC3]_L1.5轻链
<400> 308
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Ala Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 309
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP23069链1-GPC3-A_[GPC3]_H1_IgG1_PVA_/S267K重链
<400> 309
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
405 410 415
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 310
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP23069链2-GPC3-A_[GPC3]_L1.6轻链
<400> 310
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Thr Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 311
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP23070链1-GPC3-A_[GPC3]_H1_IgG1_PVA_/S267K重链
<400> 311
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
405 410 415
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 312
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP23070链2-GPC3-A_[GPC3_L1.7轻链
<400> 312
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Lys Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 313
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP23071链1-GPC3-A_[GPC3]_H1_IgG1_PVA_/S267K重链
<400> 313
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
405 410 415
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 314
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP23071链2-GPC3-A_[GPC3]_L1.8轻链
<400> 314
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Gly Gln Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 315
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP23072链1-GPC3-A_[GPC3]_H1_IgG1_PVA_/S267K重链
<400> 315
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
405 410 415
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 316
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP23072链2-GPC3-A_[GPC3]_L1.9轻链
<400> 316
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Gly Tyr Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 317
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP23073链1-GPC3-A_[GPC3]_H1_IgG1_PVA_/S267K重链
<400> 317
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
405 410 415
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 318
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP23073链2-GPC3-A_[GPC3]_L1.10轻链
<400> 318
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Gly His Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 319
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP35705链1-GPC3-A_H1.1_[GPC3]_IgG1_PVA_/S267K重链
<400> 319
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
405 410 415
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 320
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP35705链2-GPC3-A[GPC3]_L1.16轻链
<400> 320
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Ser Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Ser
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 321
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP35708链1-GPC3-A_H1.1_[GPC3]_IgG1_PVA_/S267K重链
<400> 321
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
405 410 415
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 322
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP35708链2-GPC3-A[GPC3]_L1.31轻链
<400> 322
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Tyr Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 323
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP21971链1-GPC3-A_H1_IgG1_pI(-)_同配_A_/PVA_/
S267K/L368D/K370S
<400> 323
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln
405 410 415
Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 324
<211> 485
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP21971链2-[抗CD3]_H1.30_L1.47_scFv
(GKPGS)4-Fc(216)_IgG1_C220S/PVA_/S267K/S364K/E357Q
<400> 324
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr
20 25 30
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp
50 55 60
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
65 70 75 80
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
85 90 95
Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro
115 120 125
Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly
130 135 140
Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly
145 150 155 160
Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr
165 170 175
Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg
180 185 190
Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg
195 200 205
Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly
210 215 220
Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser
225 230 235 240
Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Glu Pro
245 250 255
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro
260 265 270
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
275 280 285
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
290 295 300
Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
305 310 315 320
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
325 330 335
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
340 345 350
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala
355 360 365
Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
370 375 380
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln
385 390 395 400
Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
405 410 415
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
420 425 430
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
435 440 445
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
450 455 460
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
465 470 475 480
Leu Ser Pro Gly Lys
485
<210> 325
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP21971链3-GPC3-A_L1_[GPC3]_轻链
<400> 325
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 326
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP34364链1-GPC3-A[GPC3]_H1.1_IgG1_pI(-)_同配_A_/PVA_/
S267K/L368D/K370S
<400> 326
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln
405 410 415
Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 327
<211> 485
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP34364链2-[抗CD3]_H1.30_L1.47_scFv
(GKPGS)4-Fc(216)_IgG1_C220S/PVA_/S267K/S364K/E357Q
<400> 327
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr
20 25 30
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp
50 55 60
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
65 70 75 80
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
85 90 95
Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro
115 120 125
Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly
130 135 140
Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly
145 150 155 160
Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr
165 170 175
Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg
180 185 190
Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg
195 200 205
Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly
210 215 220
Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser
225 230 235 240
Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Glu Pro
245 250 255
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro
260 265 270
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
275 280 285
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
290 295 300
Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
305 310 315 320
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
325 330 335
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
340 345 350
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala
355 360 365
Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
370 375 380
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln
385 390 395 400
Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
405 410 415
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
420 425 430
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
435 440 445
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
450 455 460
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
465 470 475 480
Leu Ser Pro Gly Lys
485
<210> 328
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP34364链3-GPC3-A[GPC3]_L1.16_轻链
<400> 328
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Ser Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Ser
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 329
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP34365链1-GPC3-A[GPC3]_H1.1_IgG1_pI(-)_同配_A_/PVA_/
S267K/L368D/K370S
<400> 329
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln
405 410 415
Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 330
<211> 485
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP34365链2-[抗CD3]_H1.30_L1.47_scFv
(GKPGS)4-Fc(216)_IgG1_C220S/PVA_/S267K/S364K/E357Q
<400> 330
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr
20 25 30
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp
50 55 60
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
65 70 75 80
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
85 90 95
Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro
115 120 125
Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly
130 135 140
Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly
145 150 155 160
Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr
165 170 175
Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg
180 185 190
Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg
195 200 205
Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly
210 215 220
Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser
225 230 235 240
Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Glu Pro
245 250 255
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro
260 265 270
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
275 280 285
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
290 295 300
Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
305 310 315 320
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
325 330 335
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
340 345 350
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala
355 360 365
Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
370 375 380
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln
385 390 395 400
Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
405 410 415
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
420 425 430
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
435 440 445
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
450 455 460
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
465 470 475 480
Leu Ser Pro Gly Lys
485
<210> 331
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP34365链3-GPC3-A[GPC3]_L1.23_轻链
<400> 331
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Gly Asn Thr Trp Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 332
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP34367链1-GPC3-A[GPC3]_H1.1_IgG1_pI(-)_同配_A_/PVA_/
S267K/L368D/K370S
<400> 332
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln
405 410 415
Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 333
<211> 485
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP34367链2-[抗CD3]_H1.30_scFv(GKPGS)4-Fc(216)_IgG1_
C220S/PVA_/S267K/S364K/E357Q
<400> 333
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr
20 25 30
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp
50 55 60
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
65 70 75 80
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
85 90 95
Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro
115 120 125
Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly
130 135 140
Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly
145 150 155 160
Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr
165 170 175
Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg
180 185 190
Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg
195 200 205
Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly
210 215 220
Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser
225 230 235 240
Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Glu Pro
245 250 255
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro
260 265 270
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
275 280 285
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
290 295 300
Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
305 310 315 320
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
325 330 335
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
340 345 350
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala
355 360 365
Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
370 375 380
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln
385 390 395 400
Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
405 410 415
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
420 425 430
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
435 440 445
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
450 455 460
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
465 470 475 480
Leu Ser Pro Gly Lys
485
<210> 334
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP34367链3-GPC3-A[GPC3]_L1.29_轻链
<400> 334
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Gln Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 335
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP34368链1-GPC3-A[GPC3]_H1.1_IgG1_pI(-)_同配_A_/PVA_/
S267K/L368D/K370S
<400> 335
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln
405 410 415
Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 336
<211> 485
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP34368链2-GPC3-A[GPC3]_H1.1_Fab-[抗CD3]
_H1.30_L1.47_scFv(GKPGS)4-Fc(216)_IgG1_C220S
/PVA_/S267K/S364K/E357Q
<400> 336
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr
20 25 30
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp
50 55 60
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
65 70 75 80
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
85 90 95
Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro
115 120 125
Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly
130 135 140
Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly
145 150 155 160
Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr
165 170 175
Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg
180 185 190
Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg
195 200 205
Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly
210 215 220
Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser
225 230 235 240
Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Glu Pro
245 250 255
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro
260 265 270
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
275 280 285
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
290 295 300
Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
305 310 315 320
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
325 330 335
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
340 345 350
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala
355 360 365
Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
370 375 380
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln
385 390 395 400
Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
405 410 415
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
420 425 430
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
435 440 445
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
450 455 460
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
465 470 475 480
Leu Ser Pro Gly Lys
485
<210> 337
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP34368链3-GPC3-A[GPC3]_L1.31_轻链
<400> 337
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Tyr Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 338
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP35843链1-GPC3-A[GPC3]_H1.1_IgG1_pI(-)_同配_A_/PVA_/
S267K/L368D/K370S
<400> 338
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln
405 410 415
Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 339
<211> 485
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP35843链2-[抗CD3]_H1.32_L1.47_scFv
(GKPGS)4-Fc(216)_IgG1_C220S/PVA_/S267K/S364K/E357Q
<400> 339
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr
20 25 30
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp
50 55 60
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
65 70 75 80
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
85 90 95
Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro
115 120 125
Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly
130 135 140
Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly
145 150 155 160
Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr
165 170 175
Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg
180 185 190
Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg
195 200 205
Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly
210 215 220
Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser
225 230 235 240
Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Glu Pro
245 250 255
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro
260 265 270
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
275 280 285
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
290 295 300
Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
305 310 315 320
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
325 330 335
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
340 345 350
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala
355 360 365
Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
370 375 380
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln
385 390 395 400
Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
405 410 415
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
420 425 430
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
435 440 445
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
450 455 460
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
465 470 475 480
Leu Ser Pro Gly Lys
485
<210> 340
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP35843链3-GPC3-A[GPC3]_L1.16_轻链
<400> 340
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Ser Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Ser
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 341
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP36140链1-GPC3-A[GPC3]_H1.1_IgG1_pI(-)_同配_A_/PVA_/
S267K/L368D/K370S
<400> 341
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln
405 410 415
Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 342
<211> 485
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP36140链2-[抗CD3]_H1.32_L1.47_scFv
(GKPGS)4-Fc(216)_IgG1_C220S/PVA_/S267K/S364K/E357Q
<400> 342
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr
20 25 30
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp
50 55 60
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
65 70 75 80
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
85 90 95
Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro
115 120 125
Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly
130 135 140
Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly
145 150 155 160
Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr
165 170 175
Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg
180 185 190
Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg
195 200 205
Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly
210 215 220
Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser
225 230 235 240
Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Glu Pro
245 250 255
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro
260 265 270
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
275 280 285
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
290 295 300
Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
305 310 315 320
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
325 330 335
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
340 345 350
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala
355 360 365
Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
370 375 380
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln
385 390 395 400
Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
405 410 415
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
420 425 430
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
435 440 445
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
450 455 460
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
465 470 475 480
Leu Ser Pro Gly Lys
485
<210> 343
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP36140链3-GPC3-A[GPC3]_L1.31_轻链
<400> 343
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Tyr Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 344
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP36931链1-GPC3-A[GPC3]_H1.1_IgG1_pI(-)_同配_A_/PVA_/
S267K/L368D/K370S
<400> 344
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln
405 410 415
Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 345
<211> 485
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP36931链2-[抗CD3]_H1.32_L1.47_scFv
(GKPGS)4-Fc(216)_IgG1_C220S/PVA_/S267K/S364K/E357Q
<400> 345
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr
20 25 30
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp
50 55 60
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
65 70 75 80
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
85 90 95
Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro
115 120 125
Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly
130 135 140
Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly
145 150 155 160
Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr
165 170 175
Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg
180 185 190
Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg
195 200 205
Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly
210 215 220
Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser
225 230 235 240
Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Glu Pro
245 250 255
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro
260 265 270
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
275 280 285
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
290 295 300
Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
305 310 315 320
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
325 330 335
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
340 345 350
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala
355 360 365
Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
370 375 380
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln
385 390 395 400
Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
405 410 415
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
420 425 430
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
435 440 445
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
450 455 460
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
465 470 475 480
Leu Ser Pro Gly Lys
485
<210> 346
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP36931链3-GPC3-A[GPC3]_L1.65_轻链
<400> 346
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Tyr Gly Asn Thr Trp Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 347
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP36932链1-GPC3-A[GPC3]_H1.1_IgG1_pI(-)_同配_A_/PVA_/
S267K/L368D/K370S
<400> 347
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln
405 410 415
Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 348
<211> 485
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP36932链2-[抗CD3]_H1.32_L1.47_scFv
(GKPGS)4-Fc(216)_IgG1_C220S/PVA_/S267K/S364K/E357Q
<400> 348
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr
20 25 30
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp
50 55 60
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
65 70 75 80
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
85 90 95
Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro
115 120 125
Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly
130 135 140
Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly
145 150 155 160
Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr
165 170 175
Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg
180 185 190
Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg
195 200 205
Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly
210 215 220
Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser
225 230 235 240
Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Glu Pro
245 250 255
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro
260 265 270
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
275 280 285
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
290 295 300
Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
305 310 315 320
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
325 330 335
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
340 345 350
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala
355 360 365
Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
370 375 380
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln
385 390 395 400
Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
405 410 415
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
420 425 430
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
435 440 445
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
450 455 460
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
465 470 475 480
Leu Ser Pro Gly Lys
485
<210> 349
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP36932链3-GPC3-A[GPC3]_L1.66_轻链
<400> 349
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Ala Asn Thr Trp Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 350
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP36933链1-GPC3-A[GPC3]_H1.1_IgG1_pI(-)_同配_A_/PVA_/
S267K/L368D/K370S
<400> 350
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln
405 410 415
Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 351
<211> 485
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP36933链2-[抗CD3]_H1.32_L1.47_scFv
(GKPGS)4-Fc(216)_IgG1_C220S/PVA_/S267K/S364K/E357Q
<400> 351
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr
20 25 30
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp
50 55 60
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
65 70 75 80
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
85 90 95
Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro
115 120 125
Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly
130 135 140
Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly
145 150 155 160
Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr
165 170 175
Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg
180 185 190
Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg
195 200 205
Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly
210 215 220
Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser
225 230 235 240
Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Glu Pro
245 250 255
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro
260 265 270
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
275 280 285
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
290 295 300
Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
305 310 315 320
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
325 330 335
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
340 345 350
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala
355 360 365
Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
370 375 380
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln
385 390 395 400
Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
405 410 415
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
420 425 430
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
435 440 445
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
450 455 460
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
465 470 475 480
Leu Ser Pro Gly Lys
485
<210> 352
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP36933链3-GPC3-A[GPC3]_L1.67_轻链
<400> 352
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Lys Asn Thr Trp Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 353
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP36934链1-GPC3-A[GPC3]_H1.1_IgG1_pI(-)_同配_A_/PVA_/
S267K/L368D/K370S
<400> 353
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln
405 410 415
Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 354
<211> 485
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP36934链2-[抗CD3]_H1.32_L1.47_scFv
(GKPGS)4-Fc(216)_IgG1_C220S/PVA_/S267K/S364K/E357Q
<400> 354
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr
20 25 30
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp
50 55 60
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
65 70 75 80
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
85 90 95
Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro
115 120 125
Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly
130 135 140
Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly
145 150 155 160
Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr
165 170 175
Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg
180 185 190
Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg
195 200 205
Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly
210 215 220
Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser
225 230 235 240
Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Glu Pro
245 250 255
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro
260 265 270
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
275 280 285
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
290 295 300
Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
305 310 315 320
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
325 330 335
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
340 345 350
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala
355 360 365
Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
370 375 380
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln
385 390 395 400
Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
405 410 415
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
420 425 430
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
435 440 445
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
450 455 460
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
465 470 475 480
Leu Ser Pro Gly Lys
485
<210> 355
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP36934链3-GPC3-A[GPC3]_L1.68_轻链
<400> 355
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Tyr Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Gln Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 356
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP36935链1-GPC3-A[GPC3]_H1.1_IgG1_pI(-)_同配_A_/PVA_/
S267K/L368D/K370S
<400> 356
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln
405 410 415
Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 357
<211> 485
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP36935链2-[抗CD3]_H1.32_L1.47_scFv
(GKPGS)4-Fc(216)_IgG1_C220S/PVA_/S267K/S364K/E357Q
<400> 357
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr
20 25 30
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp
50 55 60
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
65 70 75 80
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
85 90 95
Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro
115 120 125
Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly
130 135 140
Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly
145 150 155 160
Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr
165 170 175
Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg
180 185 190
Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg
195 200 205
Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly
210 215 220
Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser
225 230 235 240
Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Glu Pro
245 250 255
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro
260 265 270
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
275 280 285
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
290 295 300
Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
305 310 315 320
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
325 330 335
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
340 345 350
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala
355 360 365
Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
370 375 380
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln
385 390 395 400
Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
405 410 415
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
420 425 430
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
435 440 445
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
450 455 460
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
465 470 475 480
Leu Ser Pro Gly Lys
485
<210> 358
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP36935链3-GPC3-A[GPC3]_L1.69_轻链
<400> 358
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Ala Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Gln Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 359
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP36936链1-GPC3-A[GPC3]_H1.1_IgG1_pI(-)_同配_A_/PVA_/
S267K/L368D/K370S
<400> 359
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln
405 410 415
Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 360
<211> 485
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP36936链2-[抗CD3]_H1.32_L1.47_scFv
(GKPGS)4-Fc(216)_IgG1_C220S/PVA_/S267K/S364K/E357Q
<400> 360
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr
20 25 30
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp
50 55 60
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
65 70 75 80
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
85 90 95
Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro
115 120 125
Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly
130 135 140
Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly
145 150 155 160
Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr
165 170 175
Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg
180 185 190
Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg
195 200 205
Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly
210 215 220
Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser
225 230 235 240
Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Glu Pro
245 250 255
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro
260 265 270
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
275 280 285
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
290 295 300
Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
305 310 315 320
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
325 330 335
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
340 345 350
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala
355 360 365
Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
370 375 380
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln
385 390 395 400
Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
405 410 415
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
420 425 430
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
435 440 445
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
450 455 460
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
465 470 475 480
Leu Ser Pro Gly Lys
485
<210> 361
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP36936链3-GPC3-A[GPC3]_L1.70_轻链
<400> 361
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Lys Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Gln Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 362
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP36937链1-GPC3-A[GPC3]_H1.1_IgG1_pI(-)_同配_A_/PVA_/
S267K/L368D/K370S
<400> 362
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln
405 410 415
Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 363
<211> 485
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP36937链2-[抗CD3]_H1.32_L1.47_scFv
(GKPGS)4-Fc(216)_IgG1_C220S/PVA_/S267K/S364K/E357Q
<400> 363
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr
20 25 30
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp
50 55 60
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
65 70 75 80
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
85 90 95
Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro
115 120 125
Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly
130 135 140
Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly
145 150 155 160
Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr
165 170 175
Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg
180 185 190
Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg
195 200 205
Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly
210 215 220
Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser
225 230 235 240
Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Glu Pro
245 250 255
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro
260 265 270
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
275 280 285
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
290 295 300
Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
305 310 315 320
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
325 330 335
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
340 345 350
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala
355 360 365
Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
370 375 380
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln
385 390 395 400
Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
405 410 415
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
420 425 430
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
435 440 445
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
450 455 460
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
465 470 475 480
Leu Ser Pro Gly Lys
485
<210> 364
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP36937链3-GPC3-A[GPC3]_L1.71_轻链
<400> 364
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Tyr Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Tyr Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 365
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP36938链1-GPC3-A[GPC3]_H1.1_IgG1_pI(-)_同配_A_/PVA_/
S267K/L368D/K370S
<400> 365
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln
405 410 415
Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 366
<211> 485
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP36938链2-[抗CD3]_H1.32_L1.47_scFv
(GKPGS)4-Fc(216)_IgG1_C220S/PVA_/S267K/S364K/E357Q
<400> 366
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr
20 25 30
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp
50 55 60
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
65 70 75 80
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
85 90 95
Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro
115 120 125
Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly
130 135 140
Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly
145 150 155 160
Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr
165 170 175
Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg
180 185 190
Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg
195 200 205
Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly
210 215 220
Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser
225 230 235 240
Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Glu Pro
245 250 255
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro
260 265 270
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
275 280 285
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
290 295 300
Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
305 310 315 320
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
325 330 335
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
340 345 350
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala
355 360 365
Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
370 375 380
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln
385 390 395 400
Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
405 410 415
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
420 425 430
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
435 440 445
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
450 455 460
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
465 470 475 480
Leu Ser Pro Gly Lys
485
<210> 367
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP36938链3-GPC3-A[GPC3]_L1.72_轻链
<400> 367
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Ala Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Tyr Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 368
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP36939链1-GPC3-A[GPC3]_H1.1_IgG1_pI(-)_同配_A_/PVA_/
S267K/L368D/K370S
<400> 368
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln
405 410 415
Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 369
<211> 485
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP36939链2-[抗CD3]_H1.32_L1.47_scFv
(GKPGS)4-Fc(216)_IgG1_C220S/PVA_/S267K/S364K/E357Q
<400> 369
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr
20 25 30
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp
50 55 60
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
65 70 75 80
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
85 90 95
Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro
115 120 125
Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly
130 135 140
Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly
145 150 155 160
Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr
165 170 175
Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg
180 185 190
Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg
195 200 205
Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly
210 215 220
Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser
225 230 235 240
Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Glu Pro
245 250 255
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro
260 265 270
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
275 280 285
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
290 295 300
Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
305 310 315 320
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
325 330 335
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
340 345 350
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala
355 360 365
Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
370 375 380
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln
385 390 395 400
Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
405 410 415
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
420 425 430
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
435 440 445
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
450 455 460
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
465 470 475 480
Leu Ser Pro Gly Lys
485
<210> 370
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP36939链3-GPC3-A[GPC3]_L1.73_轻链
<400> 370
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Lys Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Tyr Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 371
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP36941链1-GPC3-A[GPC3]_H1.1_IgG1_pI(-)_同配_A_/PVA_/
S267K/L368D/K370S
<400> 371
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln
405 410 415
Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 372
<211> 485
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP36941链2-[抗CD3]_H1.32_L1.47_scFv
(GKPGS)4-Fc(216)_IgG1_C220S/PVA_/S267K/S364K/E357Q
<400> 372
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr
20 25 30
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp
50 55 60
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
65 70 75 80
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
85 90 95
Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro
115 120 125
Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly
130 135 140
Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly
145 150 155 160
Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr
165 170 175
Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg
180 185 190
Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg
195 200 205
Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly
210 215 220
Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser
225 230 235 240
Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Glu Pro
245 250 255
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro
260 265 270
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
275 280 285
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
290 295 300
Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
305 310 315 320
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
325 330 335
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
340 345 350
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala
355 360 365
Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
370 375 380
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln
385 390 395 400
Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
405 410 415
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
420 425 430
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
435 440 445
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
450 455 460
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
465 470 475 480
Leu Ser Pro Gly Lys
485
<210> 373
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP36941链3-GPC3-A[GPC3]_L1.29_轻链
<400> 373
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Gln Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 374
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP38087链1-GPC3-A[GPC3]_H1.1_IgG1_pI(-)_同配_A_/PVA_/
S267K/L368D/K370S/M428L/N434S
<400> 374
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln
405 410 415
Gly Asp Val Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 375
<211> 485
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP38087链2-[抗CD3]_H1.32_L1.47_scFv
(GKPGS)4-Fc(216)_IgG1_C220S/PVA_/S267K/S364K/E357Q/M428L/N434S
<400> 375
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr
20 25 30
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp
50 55 60
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
65 70 75 80
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
85 90 95
Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro
115 120 125
Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly
130 135 140
Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly
145 150 155 160
Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr
165 170 175
Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg
180 185 190
Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg
195 200 205
Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly
210 215 220
Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser
225 230 235 240
Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Glu Pro
245 250 255
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro
260 265 270
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
275 280 285
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
290 295 300
Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
305 310 315 320
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
325 330 335
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
340 345 350
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala
355 360 365
Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
370 375 380
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln
385 390 395 400
Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
405 410 415
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
420 425 430
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
435 440 445
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
450 455 460
Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln Lys Ser Leu Ser
465 470 475 480
Leu Ser Pro Gly Lys
485
<210> 376
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP38087链3-GPC3-A[GPC3]_L1.69_轻链
<400> 376
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Ala Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Gln Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 377
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP33744链1-GPC3-A[GPC3]_H1_IgG1_pI(-)_同配_A_/PVA_/
S267K/L368D/K370S
<400> 377
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln
405 410 415
Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 378
<211> 717
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP33744链2-GPC3-A[GPC3]_H1_Fab_(G4S)2_[抗CD3]
_H1.30_L1.47_scFv(GKPGS)4_(G4S)2-Fc(222)_IgG1_C220S
/PVA_/S267K/S364K/E357Q
<400> 378
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gly
210 215 220
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
225 230 235 240
Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr
245 250 255
Phe Ser Thr Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
260 265 270
Leu Glu Trp Val Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
275 280 285
Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp
290 295 300
Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp
305 310 315 320
Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr
325 330 335
Val Ser Trp Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
340 345 350
Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser
355 360 365
Gly Lys Pro Gly Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr
370 375 380
Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly
385 390 395 400
Ala Val Thr Thr Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly
405 410 415
Lys Ser Pro Arg Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly
420 425 430
Val Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu
435 440 445
Thr Ile Ser Gly Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala
450 455 460
Leu Trp Tyr Ser Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr
465 470 475 480
Val Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Lys Thr His Thr
485 490 495
Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu
500 505 510
Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu
515 520 525
Val Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys
530 535 540
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
545 550 555 560
Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu
565 570 575
Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
580 585 590
Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
595 600 605
Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
610 615 620
Arg Glu Gln Met Thr Lys Asn Gln Val Lys Leu Thr Cys Leu Val Lys
625 630 635 640
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
645 650 655
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly
660 665 670
Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln
675 680 685
Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
690 695 700
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
705 710 715
<210> 379
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP33744链3-GPC3-A[GPC3]_L1_轻链
<400> 379
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 380
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP33745链1-GPC3-A[GPC3]_H1_IgG1_pI(-)_同配_A_/PVA_/
S267K/L368D/K370S
<400> 380
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln
405 410 415
Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 381
<211> 717
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP33745链2-GPC3-A[GPC3]_H1_Fab_(G4S)2_[抗CD3]
_L1.47_H1.30_scFv(GKPGS)4_(G4S)2-Fc(222)_IgG1_C220S
/PVA_/S267K/S364K/E357Q
<400> 381
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gly
210 215 220
Gly Gly Gly Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val
225 230 235 240
Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala
245 250 255
Val Thr Thr Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys
260 265 270
Ser Pro Arg Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val
275 280 285
Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr
290 295 300
Ile Ser Gly Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu
305 310 315 320
Trp Tyr Ser Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val
325 330 335
Leu Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser
340 345 350
Gly Lys Pro Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
355 360 365
Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
370 375 380
Thr Phe Ser Thr Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys
385 390 395 400
Gly Leu Glu Trp Val Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala
405 410 415
Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
420 425 430
Asp Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu
435 440 445
Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser
450 455 460
Tyr Val Ser Trp Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
465 470 475 480
Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Lys Thr His Thr
485 490 495
Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu
500 505 510
Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu
515 520 525
Val Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys
530 535 540
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
545 550 555 560
Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu
565 570 575
Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
580 585 590
Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
595 600 605
Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
610 615 620
Arg Glu Gln Met Thr Lys Asn Gln Val Lys Leu Thr Cys Leu Val Lys
625 630 635 640
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
645 650 655
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly
660 665 670
Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln
675 680 685
Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
690 695 700
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
705 710 715
<210> 382
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP33745链3-GPC3-A[GPC3]_L1_轻链
<400> 382
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 383
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP27259链1-GPC3-A[GPC3]_H1_IgG1_pI(-)_同配_A_/PVA_/
S267K/L368D/K370S
<400> 383
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln
405 410 415
Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 384
<211> 717
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP27259链2-GPC3-A[GPC3]_H1_Fab_(G4S)2_[抗CD3]
_H1.32_L1.47_scFv(GKPGS)4_(G4S)2-Fc(222)_IgG1_C220S
/PVA_/S267K/S364K/E357Q
<400> 384
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gly
210 215 220
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
225 230 235 240
Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr
245 250 255
Phe Ser Thr Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
260 265 270
Leu Glu Trp Val Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr
275 280 285
Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp
290 295 300
Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp
305 310 315 320
Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr
325 330 335
Val Ser Trp Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
340 345 350
Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser
355 360 365
Gly Lys Pro Gly Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr
370 375 380
Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly
385 390 395 400
Ala Val Thr Thr Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly
405 410 415
Lys Ser Pro Arg Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly
420 425 430
Val Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu
435 440 445
Thr Ile Ser Gly Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala
450 455 460
Leu Trp Tyr Ser Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr
465 470 475 480
Val Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Lys Thr His Thr
485 490 495
Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu
500 505 510
Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu
515 520 525
Val Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys
530 535 540
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
545 550 555 560
Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu
565 570 575
Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
580 585 590
Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
595 600 605
Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
610 615 620
Arg Glu Gln Met Thr Lys Asn Gln Val Lys Leu Thr Cys Leu Val Lys
625 630 635 640
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
645 650 655
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly
660 665 670
Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln
675 680 685
Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
690 695 700
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
705 710 715
<210> 385
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP27259链3-GPC3-A[GPC3]_L1_轻链
<400> 385
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 386
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP33746链1-GPC3-A[GPC3]_H1L1_IgG1_pI(-)_同配_A_/PVA_/
S267K/L368D/K370S
<400> 386
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln
405 410 415
Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 387
<211> 717
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP33746链2-GPC3-A[GPC3]_H1_Fab_(G4S)2_[抗CD3]
_L1.47_H1.32_scFv(GKPGS)4_(G4S)2-Fc(222)_IgG1_C220S
/PVA_/S267K/S364K/E357Q
<400> 387
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gly
210 215 220
Gly Gly Gly Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val
225 230 235 240
Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala
245 250 255
Val Thr Thr Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys
260 265 270
Ser Pro Arg Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val
275 280 285
Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr
290 295 300
Ile Ser Gly Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu
305 310 315 320
Trp Tyr Ser Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val
325 330 335
Leu Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser
340 345 350
Gly Lys Pro Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
355 360 365
Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
370 375 380
Thr Phe Ser Thr Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys
385 390 395 400
Gly Leu Glu Trp Val Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala
405 410 415
Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
420 425 430
Asp Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu
435 440 445
Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser
450 455 460
Tyr Val Ser Trp Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
465 470 475 480
Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Lys Thr His Thr
485 490 495
Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu
500 505 510
Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu
515 520 525
Val Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys
530 535 540
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
545 550 555 560
Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu
565 570 575
Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
580 585 590
Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
595 600 605
Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
610 615 620
Arg Glu Gln Met Thr Lys Asn Gln Val Lys Leu Thr Cys Leu Val Lys
625 630 635 640
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
645 650 655
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly
660 665 670
Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln
675 680 685
Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
690 695 700
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
705 710 715
<210> 388
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP33746链3-GPC3-A[GPC3]_L1_轻链
<400> 388
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 389
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP34919链1-GPC3-A[GPC3]_H1.1_IgG1_pI(-)_同配_A_/PVA_/
S267K/L368D/K370S
<400> 389
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln
405 410 415
Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 390
<211> 717
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP34919链2-GPC3-A[GPC3]_H1.1_Fab_(G4S)2_[抗CD3]
_L1.47_H1.32_scFv(GKPGS)4_(G4S)2-Fc(222)_IgG1_C220S
/PVA_/S267K/S364K/E357Q
<400> 390
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gly
210 215 220
Gly Gly Gly Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val
225 230 235 240
Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala
245 250 255
Val Thr Thr Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys
260 265 270
Ser Pro Arg Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val
275 280 285
Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr
290 295 300
Ile Ser Gly Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu
305 310 315 320
Trp Tyr Ser Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val
325 330 335
Leu Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser
340 345 350
Gly Lys Pro Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
355 360 365
Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
370 375 380
Thr Phe Ser Thr Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys
385 390 395 400
Gly Leu Glu Trp Val Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala
405 410 415
Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
420 425 430
Asp Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu
435 440 445
Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser
450 455 460
Tyr Val Ser Trp Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
465 470 475 480
Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Lys Thr His Thr
485 490 495
Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu
500 505 510
Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu
515 520 525
Val Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys
530 535 540
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
545 550 555 560
Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu
565 570 575
Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
580 585 590
Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
595 600 605
Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
610 615 620
Arg Glu Gln Met Thr Lys Asn Gln Val Lys Leu Thr Cys Leu Val Lys
625 630 635 640
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
645 650 655
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly
660 665 670
Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln
675 680 685
Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
690 695 700
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
705 710 715
<210> 391
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP34919链3-GPC3-A[GPC3]_L1.6_轻链
<400> 391
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Thr Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 392
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP34920链1-GPC3-A[GPC3]_H1.1_IgG1_pI(-)_同配_A_/PVA_/
S267K/L368D/K370S
<400> 392
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln
405 410 415
Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 393
<211> 717
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP34920链2-GPC3-A[GPC3]_H1.1_Fab_(G4S)2_[抗CD3]
_L1.47_H1.32_scFv(GKPGS)4_(G4S)2-Fc(222)_IgG1_C220S
/PVA_/S267K/S364K/E357Q
<400> 393
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gly
210 215 220
Gly Gly Gly Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val
225 230 235 240
Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala
245 250 255
Val Thr Thr Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys
260 265 270
Ser Pro Arg Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val
275 280 285
Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr
290 295 300
Ile Ser Gly Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu
305 310 315 320
Trp Tyr Ser Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val
325 330 335
Leu Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser
340 345 350
Gly Lys Pro Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
355 360 365
Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
370 375 380
Thr Phe Ser Thr Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys
385 390 395 400
Gly Leu Glu Trp Val Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala
405 410 415
Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
420 425 430
Asp Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu
435 440 445
Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser
450 455 460
Tyr Val Ser Trp Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
465 470 475 480
Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Lys Thr His Thr
485 490 495
Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu
500 505 510
Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu
515 520 525
Val Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys
530 535 540
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
545 550 555 560
Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu
565 570 575
Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
580 585 590
Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
595 600 605
Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
610 615 620
Arg Glu Gln Met Thr Lys Asn Gln Val Lys Leu Thr Cys Leu Val Lys
625 630 635 640
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
645 650 655
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly
660 665 670
Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln
675 680 685
Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
690 695 700
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
705 710 715
<210> 394
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP34920链3-GPC3-A[GPC3]_L1.16_轻链
<400> 394
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Ser Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Ser
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 395
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP34921链1-GPC3-A[GPC3]_H1.1_IgG1_pI(-)_同配_A_/PVA_/
S267K/L368D/K370S
<400> 395
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln
405 410 415
Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 396
<211> 717
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP34921链2-GPC3-A[GPC3]_H1.1_Fab_(G4S)2_[抗CD3]
_L1.47_H1.32_scFv(GKPGS)4_(G4S)2-Fc(222)_IgG1_C220S
/PVA_/S267K/S364K/E357Q
<400> 396
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gly
210 215 220
Gly Gly Gly Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val
225 230 235 240
Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala
245 250 255
Val Thr Thr Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys
260 265 270
Ser Pro Arg Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val
275 280 285
Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr
290 295 300
Ile Ser Gly Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu
305 310 315 320
Trp Tyr Ser Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val
325 330 335
Leu Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser
340 345 350
Gly Lys Pro Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
355 360 365
Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
370 375 380
Thr Phe Ser Thr Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys
385 390 395 400
Gly Leu Glu Trp Val Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala
405 410 415
Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
420 425 430
Asp Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu
435 440 445
Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser
450 455 460
Tyr Val Ser Trp Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
465 470 475 480
Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Lys Thr His Thr
485 490 495
Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu
500 505 510
Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu
515 520 525
Val Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys
530 535 540
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
545 550 555 560
Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu
565 570 575
Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
580 585 590
Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
595 600 605
Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
610 615 620
Arg Glu Gln Met Thr Lys Asn Gln Val Lys Leu Thr Cys Leu Val Lys
625 630 635 640
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
645 650 655
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly
660 665 670
Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln
675 680 685
Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
690 695 700
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
705 710 715
<210> 397
<211> 93
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP34921链3-GPC3-A[GPC3]_L1.23_轻链
<400> 397
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Gly Asn Thr Trp Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys
85 90
<210> 398
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP34922链1-GPC3-A[GPC3]_H1.1_IgG1_pI(-)_同配_A_/PVA_/
S267K/L368D/K370S
<400> 398
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln
405 410 415
Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 399
<211> 717
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP34922链2-GPC3-A[GPC3]_H1.1_Fab_(G4S)2_[抗CD3]
_L1.47_H1.32_scFv(GKPGS)4_(G4S)2-Fc(222)_IgG1_C220S
/PVA_/S267K/S364K/E357Q
<400> 399
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gly
210 215 220
Gly Gly Gly Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val
225 230 235 240
Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala
245 250 255
Val Thr Thr Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys
260 265 270
Ser Pro Arg Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val
275 280 285
Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr
290 295 300
Ile Ser Gly Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu
305 310 315 320
Trp Tyr Ser Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val
325 330 335
Leu Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser
340 345 350
Gly Lys Pro Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
355 360 365
Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
370 375 380
Thr Phe Ser Thr Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys
385 390 395 400
Gly Leu Glu Trp Val Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala
405 410 415
Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
420 425 430
Asp Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu
435 440 445
Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser
450 455 460
Tyr Val Ser Trp Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
465 470 475 480
Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Lys Thr His Thr
485 490 495
Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu
500 505 510
Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu
515 520 525
Val Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys
530 535 540
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
545 550 555 560
Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu
565 570 575
Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
580 585 590
Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
595 600 605
Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
610 615 620
Arg Glu Gln Met Thr Lys Asn Gln Val Lys Leu Thr Cys Leu Val Lys
625 630 635 640
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
645 650 655
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly
660 665 670
Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln
675 680 685
Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
690 695 700
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
705 710 715
<210> 400
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP34922链3-GPC3-A[GPC3]_L1.29_轻链
<400> 400
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Gln Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 401
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP34923链1-GPC3-A[GPC3]_H1.1_IgG1_pI(-)_同配_A_/PVA_/
S267K/L368D/K370S
<400> 401
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln
405 410 415
Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 402
<211> 717
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP34923链2-GPC3-A[GPC3]_H1.1_Fab_(G4S)2_[抗CD3]
_L1.47_H1.32_scFv(GKPGS)4_(G4S)2-Fc(222)_IgG1_C220S
/PVA_/S267K/S364K/E357Q
<400> 402
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gly
210 215 220
Gly Gly Gly Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val
225 230 235 240
Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala
245 250 255
Val Thr Thr Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys
260 265 270
Ser Pro Arg Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val
275 280 285
Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr
290 295 300
Ile Ser Gly Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu
305 310 315 320
Trp Tyr Ser Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val
325 330 335
Leu Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser
340 345 350
Gly Lys Pro Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
355 360 365
Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
370 375 380
Thr Phe Ser Thr Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys
385 390 395 400
Gly Leu Glu Trp Val Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala
405 410 415
Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
420 425 430
Asp Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu
435 440 445
Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser
450 455 460
Tyr Val Ser Trp Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
465 470 475 480
Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Lys Thr His Thr
485 490 495
Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu
500 505 510
Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu
515 520 525
Val Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys
530 535 540
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
545 550 555 560
Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu
565 570 575
Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
580 585 590
Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
595 600 605
Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
610 615 620
Arg Glu Gln Met Thr Lys Asn Gln Val Lys Leu Thr Cys Leu Val Lys
625 630 635 640
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
645 650 655
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly
660 665 670
Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln
675 680 685
Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
690 695 700
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
705 710 715
<210> 403
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP34923链3-GPC3-A[GPC3]_L1.31_轻链
<400> 403
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Tyr Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 404
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP35840链1-GPC3-A[GPC3]_H1_IgG1_pI(-)_同配_A_/PVA_/
S267K/L368D/K370S
<400> 404
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln
405 410 415
Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 405
<211> 717
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP35840链2-GPC3-A[GPC3]_H1_Fab_(G4S)2_[抗CD3]
_H1.32_L1.47_scFv(GKPGS)4_(G4S)2-Fc(222)_IgG1_C220S
/PVA_/S267K/S364K/E357Q
<400> 405
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gly
210 215 220
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
225 230 235 240
Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr
245 250 255
Phe Ser Thr Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
260 265 270
Leu Glu Trp Val Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr
275 280 285
Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp
290 295 300
Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp
305 310 315 320
Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr
325 330 335
Val Ser Trp Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
340 345 350
Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser
355 360 365
Gly Lys Pro Gly Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr
370 375 380
Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly
385 390 395 400
Ala Val Thr Thr Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly
405 410 415
Lys Ser Pro Arg Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly
420 425 430
Val Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu
435 440 445
Thr Ile Ser Gly Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala
450 455 460
Leu Trp Tyr Ser Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr
465 470 475 480
Val Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Lys Thr His Thr
485 490 495
Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu
500 505 510
Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu
515 520 525
Val Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys
530 535 540
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
545 550 555 560
Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu
565 570 575
Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
580 585 590
Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
595 600 605
Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
610 615 620
Arg Glu Gln Met Thr Lys Asn Gln Val Lys Leu Thr Cys Leu Val Lys
625 630 635 640
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
645 650 655
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly
660 665 670
Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln
675 680 685
Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
690 695 700
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
705 710 715
<210> 406
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP35840链3-GPC3-A[GPC3]_L1.16_轻链
<400> 406
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Ser Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Ser
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 407
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP35840链3-GPC3-A[GPC3]_L1.16_轻链
<400> 407
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Ser Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Ser
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 408
<211> 672
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP37246链1-GPC3-A[GPC3]_H1.1_IgG1_pI(-)_同配_A_/PVA_/
S267K/L368D/K370S
<400> 408
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gly
210 215 220
Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys
225 230 235 240
Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr
245 250 255
Phe Thr Asp Tyr Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly
260 265 270
Leu Glu Trp Met Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr
275 280 285
Ser Gln Lys Phe Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile
290 295 300
Ser Thr Ala Tyr Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala
305 310 315 320
Val Tyr Tyr Cys Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly
325 330 335
Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
340 345 350
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
355 360 365
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
370 375 380
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
385 390 395 400
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
405 410 415
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
420 425 430
Ser Asp Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys
435 440 445
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser
450 455 460
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg
465 470 475 480
Thr Pro Glu Val Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro
485 490 495
Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala
500 505 510
Lys Thr Lys Pro Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val
515 520 525
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr
530 535 540
Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr
545 550 555 560
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu
565 570 575
Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys
580 585 590
Asp Val Ser Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
595 600 605
Asp Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp
610 615 620
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser
625 630 635 640
Arg Trp Glu Gln Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala
645 650 655
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
660 665 670
<210> 409
<211> 485
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP37246链2-GPC3-A[GPC3]_H1.1_Fab-[抗CD3]
_H1.32_L1.47_scFv(GKPGS)4-Fc(216)_IgG1_C220S
/PVA_/S267K/S364K/E357Q
<400> 409
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr
20 25 30
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp
50 55 60
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
65 70 75 80
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
85 90 95
Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro
115 120 125
Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly
130 135 140
Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly
145 150 155 160
Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr
165 170 175
Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg
180 185 190
Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg
195 200 205
Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly
210 215 220
Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser
225 230 235 240
Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Glu Pro
245 250 255
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro
260 265 270
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
275 280 285
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
290 295 300
Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
305 310 315 320
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
325 330 335
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
340 345 350
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala
355 360 365
Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
370 375 380
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln
385 390 395 400
Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
405 410 415
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
420 425 430
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
435 440 445
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
450 455 460
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
465 470 475 480
Leu Ser Pro Gly Lys
485
<210> 410
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP37246链3-GPC3-A[GPC3]_L1.16_轻链
<400> 410
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Ser Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Ser
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 411
<211> 672
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP37247链1-GPC3-A[GPC3]_H1.1_IgG1_pI(-)_同配_A_/PVA_/
S267K/L368D/K370S
<400> 411
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gly
210 215 220
Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys
225 230 235 240
Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr
245 250 255
Phe Thr Asp Tyr Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly
260 265 270
Leu Glu Trp Met Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr
275 280 285
Ser Gln Lys Phe Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile
290 295 300
Ser Thr Ala Tyr Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala
305 310 315 320
Val Tyr Tyr Cys Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly
325 330 335
Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
340 345 350
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
355 360 365
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
370 375 380
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
385 390 395 400
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
405 410 415
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
420 425 430
Ser Asp Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys
435 440 445
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser
450 455 460
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg
465 470 475 480
Thr Pro Glu Val Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro
485 490 495
Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala
500 505 510
Lys Thr Lys Pro Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val
515 520 525
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr
530 535 540
Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr
545 550 555 560
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu
565 570 575
Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys
580 585 590
Asp Val Ser Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
595 600 605
Asp Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp
610 615 620
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser
625 630 635 640
Arg Trp Glu Gln Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala
645 650 655
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
660 665 670
<210> 412
<211> 485
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP37247链2-GPC3-A[GPC3]_H1.1_Fab-[抗CD3]
_L1.47_H1.32_scFv(GKPGS)4-Fc(216)_IgG1_C220S
/PVA_/S267K/S364K/E357Q
<400> 412
Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly
1 5 10 15
Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser
20 25 30
Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly
35 40 45
Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe
50 55 60
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala
65 70 75 80
Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn
85 90 95
His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Lys Pro
100 105 110
Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly
115 120 125
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
130 135 140
Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr
145 150 155 160
Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
165 170 175
Val Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala
180 185 190
Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
195 200 205
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
210 215 220
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp
225 230 235 240
Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Glu Pro
245 250 255
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro
260 265 270
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
275 280 285
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
290 295 300
Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
305 310 315 320
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
325 330 335
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
340 345 350
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala
355 360 365
Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
370 375 380
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln
385 390 395 400
Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
405 410 415
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
420 425 430
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
435 440 445
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
450 455 460
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
465 470 475 480
Leu Ser Pro Gly Lys
485
<210> 413
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP37247链3-GPC3-A[GPC3]_L1.16_轻链
<400> 413
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Ser Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Ser
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 414
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP38086链1-GPC3-A[GPC3]_H1.1_IgG1_pI(-)_同配_A_/PVA_/
S267K/L368D/K370S/M428L/N434S
<400> 414
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln
405 410 415
Gly Asp Val Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 415
<211> 717
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP38086链2-GPC3-A[GPC3]_H1.1_Fab_(G4S)2_[抗CD3]
_L1.47_H1.32_scFv(GKPGS)4_(G4S)2-Fc(222)_IgG1_C220S
/PVA_/S267K/S364K/E357Q/M428L/N434S
<400> 415
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gly
210 215 220
Gly Gly Gly Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val
225 230 235 240
Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala
245 250 255
Val Thr Thr Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys
260 265 270
Ser Pro Arg Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val
275 280 285
Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr
290 295 300
Ile Ser Gly Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu
305 310 315 320
Trp Tyr Ser Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val
325 330 335
Leu Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser
340 345 350
Gly Lys Pro Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
355 360 365
Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
370 375 380
Thr Phe Ser Thr Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys
385 390 395 400
Gly Leu Glu Trp Val Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala
405 410 415
Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
420 425 430
Asp Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu
435 440 445
Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser
450 455 460
Tyr Val Ser Trp Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
465 470 475 480
Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Lys Thr His Thr
485 490 495
Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu
500 505 510
Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu
515 520 525
Val Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys
530 535 540
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
545 550 555 560
Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu
565 570 575
Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
580 585 590
Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
595 600 605
Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
610 615 620
Arg Glu Gln Met Thr Lys Asn Gln Val Lys Leu Thr Cys Leu Val Lys
625 630 635 640
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
645 650 655
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly
660 665 670
Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln
675 680 685
Gln Gly Asn Val Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser
690 695 700
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
705 710 715
<210> 416
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP38086链3-GPC3-A[GPC3]_L1.16_轻链
<400> 416
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Ser Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Ser
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 417
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP33747链1-GPC3-A[GPC3]_H1_IgG1_pI(-)_同配_A_/PVA_/
S267K/L368D/K370S
<400> 417
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln
405 410 415
Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 418
<211> 713
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP33747链2-GPC3-A[GPC3]_H1_Fab_(G4S)2_[抗CD3]
_L1.47_H1.89_scFv(GKPGS)4-Fc(216)_IgG1_C220S/PVA_/S 267K/S364K/E357Q
<400> 418
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gly
210 215 220
Gly Gly Gly Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val
225 230 235 240
Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala
245 250 255
Val Thr Thr Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys
260 265 270
Ser Pro Arg Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val
275 280 285
Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr
290 295 300
Ile Ser Gly Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu
305 310 315 320
Trp Tyr Ser Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val
325 330 335
Leu Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser
340 345 350
Gly Lys Pro Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
355 360 365
Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
370 375 380
Thr Phe Ser Thr Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys
385 390 395 400
Gly Leu Glu Trp Val Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala
405 410 415
Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
420 425 430
Asp Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu
435 440 445
Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asp Glu
450 455 460
Tyr Val Ser Trp Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
465 470 475 480
Ser Ser Glu Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys
485 490 495
Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
500 505 510
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
515 520 525
Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
530 535 540
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
545 550 555 560
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
565 570 575
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
580 585 590
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
595 600 605
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met
610 615 620
Thr Lys Asn Gln Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
625 630 635 640
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
645 650 655
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
660 665 670
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val
675 680 685
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
690 695 700
Lys Ser Leu Ser Leu Ser Pro Gly Lys
705 710
<210> 419
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP33747链3-GPC3-A[GPC3]_L1_轻链
<400> 419
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 420
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP35841链1-GPC3-A[GPC3]_H1.1_IgG1_pI(-)_同配_A_/PVA_/
S267K/L368D/K370S
<400> 420
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln
405 410 415
Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 421
<211> 713
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP35841链2-GPC3-A[GPC3]_H1.1_Fab_(G4S)2_[抗CD3]
_L1.47_H1.89_scFv(GKPGS)4_(G4S)2-Fc(222)_IgG1_C220S
/PVA_/S267K/S364K/E357Q
<400> 421
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gly
210 215 220
Gly Gly Gly Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val
225 230 235 240
Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala
245 250 255
Val Thr Thr Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys
260 265 270
Ser Pro Arg Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val
275 280 285
Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr
290 295 300
Ile Ser Gly Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu
305 310 315 320
Trp Tyr Ser Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val
325 330 335
Leu Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser
340 345 350
Gly Lys Pro Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
355 360 365
Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
370 375 380
Thr Phe Ser Thr Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys
385 390 395 400
Gly Leu Glu Trp Val Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala
405 410 415
Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
420 425 430
Asp Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu
435 440 445
Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asp Glu
450 455 460
Tyr Val Ser Trp Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
465 470 475 480
Ser Ser Glu Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys
485 490 495
Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
500 505 510
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
515 520 525
Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
530 535 540
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
545 550 555 560
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
565 570 575
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
580 585 590
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
595 600 605
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met
610 615 620
Thr Lys Asn Gln Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
625 630 635 640
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
645 650 655
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
660 665 670
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val
675 680 685
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
690 695 700
Lys Ser Leu Ser Leu Ser Pro Gly Lys
705 710
<210> 422
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP35841链3-GPC3-A[GPC3]_L1.16_轻链
<400> 422
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Ser Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Ser
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 423
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP37624链1-GPC3-A[GPC3]_H1.1_IgG1_pI(-)_同配_A_/PVA_/
S267K/L368D/K370S
<400> 423
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln
405 410 415
Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 424
<211> 713
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP37624链2-GPC3-A[GPC3]_H1.1_Fab_(G4S)2_[抗CD3]
_L1.47_H1.89_scFv(GKPGS)4_(G4S)2-Fc(222)_IgG1_C220S
/PVA_/S267K/S364K/E357Q
<400> 424
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gly
210 215 220
Gly Gly Gly Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val
225 230 235 240
Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala
245 250 255
Val Thr Thr Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys
260 265 270
Ser Pro Arg Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val
275 280 285
Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr
290 295 300
Ile Ser Gly Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu
305 310 315 320
Trp Tyr Ser Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val
325 330 335
Leu Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser
340 345 350
Gly Lys Pro Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
355 360 365
Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
370 375 380
Thr Phe Ser Thr Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys
385 390 395 400
Gly Leu Glu Trp Val Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala
405 410 415
Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
420 425 430
Asp Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu
435 440 445
Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asp Glu
450 455 460
Tyr Val Ser Trp Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
465 470 475 480
Ser Ser Glu Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys
485 490 495
Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
500 505 510
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
515 520 525
Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
530 535 540
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
545 550 555 560
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
565 570 575
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
580 585 590
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
595 600 605
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met
610 615 620
Thr Lys Asn Gln Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
625 630 635 640
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
645 650 655
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
660 665 670
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val
675 680 685
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
690 695 700
Lys Ser Leu Ser Leu Ser Pro Gly Lys
705 710
<210> 425
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP37624链3-GPC3-A[GPC3]_L1.16_轻链
<400> 425
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Ser Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Ser
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 426
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP37625链1-GPC3-A[GPC3]_H1.1_Fab-GPC3-
A[GPC3]_IgG1_pI(-)_同配_A_/PVA_/S267K/L368D/K370S
<400> 426
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln
405 410 415
Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 427
<211> 713
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP37625链2-GPC3-A[GPC3]_H1.1_L1.69_Fab_(G4S)2_[抗CD3]
_L1.47_H1.89_scFv(GKPGS)4-Fc(216)_IgG1_C220S
/PVA_/S267K/S364K/E357Q
<400> 427
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gly
210 215 220
Gly Gly Gly Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val
225 230 235 240
Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala
245 250 255
Val Thr Thr Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys
260 265 270
Ser Pro Arg Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val
275 280 285
Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr
290 295 300
Ile Ser Gly Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu
305 310 315 320
Trp Tyr Ser Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val
325 330 335
Leu Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser
340 345 350
Gly Lys Pro Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
355 360 365
Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
370 375 380
Thr Phe Ser Thr Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys
385 390 395 400
Gly Leu Glu Trp Val Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala
405 410 415
Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
420 425 430
Asp Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu
435 440 445
Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asp Glu
450 455 460
Tyr Val Ser Trp Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
465 470 475 480
Ser Ser Glu Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys
485 490 495
Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
500 505 510
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
515 520 525
Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
530 535 540
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
545 550 555 560
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
565 570 575
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
580 585 590
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
595 600 605
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met
610 615 620
Thr Lys Asn Gln Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
625 630 635 640
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
645 650 655
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
660 665 670
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val
675 680 685
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
690 695 700
Lys Ser Leu Ser Leu Ser Pro Gly Lys
705 710
<210> 428
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP37625链3-GPC3-A[GPC3]_L1.69_轻链
<400> 428
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Ala Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Gln Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 429
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP37626链1-GPC3-A[GPC3]_H1.1_IgG1_pI(-)_同配_A_/PVA_/
S267K/L368D/K370S
<400> 429
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln
405 410 415
Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 430
<211> 713
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP37626链2-GPC3-A[GPC3]_H1.1_Fab_(G4S)2_[抗CD3]
_L1.47_H1.89_scFv(GKPGS)4_(G4S)2-Fc(222)_IgG1_C220S
/PVA_/S267K/S364K/E357Q
<400> 430
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gly
210 215 220
Gly Gly Gly Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val
225 230 235 240
Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala
245 250 255
Val Thr Thr Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys
260 265 270
Ser Pro Arg Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val
275 280 285
Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr
290 295 300
Ile Ser Gly Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu
305 310 315 320
Trp Tyr Ser Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val
325 330 335
Leu Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser
340 345 350
Gly Lys Pro Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
355 360 365
Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
370 375 380
Thr Phe Ser Thr Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys
385 390 395 400
Gly Leu Glu Trp Val Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala
405 410 415
Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
420 425 430
Asp Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu
435 440 445
Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asp Glu
450 455 460
Tyr Val Ser Trp Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
465 470 475 480
Ser Ser Glu Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys
485 490 495
Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
500 505 510
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
515 520 525
Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
530 535 540
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
545 550 555 560
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
565 570 575
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
580 585 590
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
595 600 605
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met
610 615 620
Thr Lys Asn Gln Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
625 630 635 640
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
645 650 655
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
660 665 670
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val
675 680 685
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
690 695 700
Lys Ser Leu Ser Leu Ser Pro Gly Lys
705 710
<210> 431
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP37626链3-GPC3-A[GPC3]_L1.73_轻链
<400> 431
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Lys Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Tyr Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 432
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP38232链1-GPC3-A[GPC3]_H1.1_IgG1_pI(-)_同配_A_/PVA_/
S267K/L368D/K370S/M428L/N434S
<400> 432
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln
405 410 415
Gly Asp Val Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 433
<211> 713
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP38232链2-GPC3-A[GPC3]_H1.1_Fab_(G4S)2_[抗CD3]
_L1.47_H1.89_scFv(GKPGS)4-Fc(216)_IgG1_C220S
/PVA_/S267K/S364K/E357Q/M428L/N434S
<400> 433
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gly
210 215 220
Gly Gly Gly Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val
225 230 235 240
Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala
245 250 255
Val Thr Thr Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys
260 265 270
Ser Pro Arg Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val
275 280 285
Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr
290 295 300
Ile Ser Gly Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu
305 310 315 320
Trp Tyr Ser Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val
325 330 335
Leu Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser
340 345 350
Gly Lys Pro Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
355 360 365
Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
370 375 380
Thr Phe Ser Thr Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys
385 390 395 400
Gly Leu Glu Trp Val Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala
405 410 415
Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
420 425 430
Asp Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu
435 440 445
Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asp Glu
450 455 460
Tyr Val Ser Trp Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
465 470 475 480
Ser Ser Glu Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys
485 490 495
Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
500 505 510
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
515 520 525
Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
530 535 540
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
545 550 555 560
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
565 570 575
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
580 585 590
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
595 600 605
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met
610 615 620
Thr Lys Asn Gln Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
625 630 635 640
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
645 650 655
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
660 665 670
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val
675 680 685
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
690 695 700
Lys Ser Leu Ser Leu Ser Pro Gly Lys
705 710
<210> 434
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP38232链3-GPC3-A[GPC3]_L1.69_轻链
<400> 434
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Ala Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Gln Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 435
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP37430链1-GPC3-A[GPC3]_H1.1_IgG1_pI(-)_同配_A_/PVA_/
S267K/L368D/K370S
<400> 435
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln
405 410 415
Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 436
<211> 717
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP37430链2-GPC3-A[GPC3]_H1.1_Fab_(G4S)2_[抗CD3]
_L1.47_H1.32_scFv(GKPGS)4_(G4S)2-Fc(222)_IgG1_C220S
/PVA_/S267K/S364K/E357Q
<400> 436
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gly
210 215 220
Gly Gly Gly Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val
225 230 235 240
Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala
245 250 255
Val Thr Thr Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys
260 265 270
Ser Pro Arg Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val
275 280 285
Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr
290 295 300
Ile Ser Gly Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu
305 310 315 320
Trp Tyr Ser Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val
325 330 335
Leu Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser
340 345 350
Gly Lys Pro Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
355 360 365
Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
370 375 380
Thr Phe Ser Thr Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys
385 390 395 400
Gly Leu Glu Trp Val Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala
405 410 415
Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
420 425 430
Asp Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu
435 440 445
Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser
450 455 460
Tyr Val Ser Trp Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
465 470 475 480
Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Lys Thr His Thr
485 490 495
Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu
500 505 510
Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu
515 520 525
Val Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys
530 535 540
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
545 550 555 560
Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu
565 570 575
Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
580 585 590
Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
595 600 605
Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
610 615 620
Arg Glu Gln Met Thr Lys Asn Gln Val Lys Leu Thr Cys Leu Val Lys
625 630 635 640
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
645 650 655
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly
660 665 670
Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln
675 680 685
Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
690 695 700
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
705 710 715
<210> 437
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP37430链3-GPC3-A[GPC3]_L1.69_轻链
<400> 437
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Ala Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Gln Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 438
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP37433链1-GPC3-A[GPC3]_H1.1_IgG1_pI(-)_同配_A_/PVA_/
S267K/L368D/K370S
<400> 438
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln
405 410 415
Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 439
<211> 717
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP37433链2-GPC3-A[GPC3]_H1.1_Fab_(G4S)2_[抗CD3]
_L1.47_H1.32_scFv(GKPGS)4_(G4S)2-Fc(222)_IgG1_C220S
/PVA_/S267K/S364K/E357Q
<400> 439
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Glu Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gly
210 215 220
Gly Gly Gly Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val
225 230 235 240
Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala
245 250 255
Val Thr Thr Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys
260 265 270
Ser Pro Arg Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val
275 280 285
Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr
290 295 300
Ile Ser Gly Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu
305 310 315 320
Trp Tyr Ser Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val
325 330 335
Leu Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser
340 345 350
Gly Lys Pro Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
355 360 365
Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
370 375 380
Thr Phe Ser Thr Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys
385 390 395 400
Gly Leu Glu Trp Val Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala
405 410 415
Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
420 425 430
Asp Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu
435 440 445
Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser
450 455 460
Tyr Val Ser Trp Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
465 470 475 480
Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Lys Thr His Thr
485 490 495
Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu
500 505 510
Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu
515 520 525
Val Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys
530 535 540
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
545 550 555 560
Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu
565 570 575
Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
580 585 590
Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
595 600 605
Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
610 615 620
Arg Glu Gln Met Thr Lys Asn Gln Val Lys Leu Thr Cys Leu Val Lys
625 630 635 640
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
645 650 655
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly
660 665 670
Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln
675 680 685
Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
690 695 700
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
705 710 715
<210> 440
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP37433链3-GPC3-A[GPC3]_L1.73_轻链
<400> 440
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Lys Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Tyr Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 441
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP33748链1-GPC3-A[GPC3]_H1_IgG1_pI(-)_同配_A_/PVA_/
S267K/L368D/K370S
<400> 441
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln
405 410 415
Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 442
<211> 717
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP33748链2-GPC3-A[GPC3]_H1_Fab_(G4S)2_[抗CD3]
_L1.47_H1.33_scFv(GKPGS)4_(G4S)2-Fc(222)_IgG1_C220S
/PVA_/S267K/S364K/E357Q
<400> 442
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Leu Asp Pro Lys Thr Gly Asp Thr Ala Tyr Ser Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gly
210 215 220
Gly Gly Gly Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val
225 230 235 240
Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala
245 250 255
Val Thr Thr Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys
260 265 270
Ser Pro Arg Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val
275 280 285
Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr
290 295 300
Ile Ser Gly Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu
305 310 315 320
Trp Tyr Ser Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val
325 330 335
Leu Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser
340 345 350
Gly Lys Pro Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
355 360 365
Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
370 375 380
Thr Phe Ser Thr Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys
385 390 395 400
Gly Leu Glu Trp Val Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala
405 410 415
Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
420 425 430
Asp Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu
435 440 445
Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser
450 455 460
Tyr Val Ser Trp Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
465 470 475 480
Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Lys Thr His Thr
485 490 495
Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu
500 505 510
Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu
515 520 525
Val Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys
530 535 540
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
545 550 555 560
Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu
565 570 575
Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
580 585 590
Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
595 600 605
Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
610 615 620
Arg Glu Gln Met Thr Lys Asn Gln Val Lys Leu Thr Cys Leu Val Lys
625 630 635 640
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
645 650 655
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly
660 665 670
Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln
675 680 685
Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
690 695 700
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
705 710 715
<210> 443
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP33748链3-GPC3-A[GPC3]_L1_轻链
<400> 443
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu His Trp Tyr Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Phe Cys Ser Gln Asn
85 90 95
Thr His Val Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 444
<211> 444
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP31308链1-GCH065[GPC3]_H0_Fab_ IgG1_pI
(-)_同配_A_PVA_/S267K/L368D/K370S
<400> 444
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Thr Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Glu Met His Trp Ile Arg Gln Pro Pro Gly Glu Gly Leu Glu Trp Ile
35 40 45
Gly Ala Ile Asp Gly Pro Thr Pro Asp Thr Ala Tyr Ser Glu Lys Phe
50 55 60
Lys Gly Arg Val Thr Leu Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Thr Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Phe Tyr Ser Tyr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr Lys
195 200 205
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln
405 410 415
Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 445
<211> 451
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP31308链2- TR01H113[CD3]_H0_Fab-Fc(222)_IgG1_PVA_/
S267K/S364K/E357Q (222)_IgG1_PVA_/S267K/S364K/E357Q
<400> 445
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn Ala
20 25 30
Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Gln Ile Lys Asp Lys Ser Gln Asn Tyr Ala Thr Tyr Val Ala Glu
50 55 60
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Ala Asp Ser Lys Asn Ser
65 70 75 80
Ile Tyr Leu Gln Met Asn Ser Leu Lys Thr Glu Asp Thr Ala Val Tyr
85 90 95
Tyr Cys Arg Tyr Val His Tyr Ala Ala Gly Tyr Gly Val Asp Ile Trp
100 105 110
Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro
115 120 125
Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr
130 135 140
Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr
145 150 155 160
Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro
165 170 175
Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr
180 185 190
Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn
195 200 205
His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser
210 215 220
Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala
225 230 235 240
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
245 250 255
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Lys His
260 265 270
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
275 280 285
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
290 295 300
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
305 310 315 320
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
325 330 335
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
340 345 350
Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln Val Lys
355 360 365
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
370 375 380
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
385 390 395 400
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
405 410 415
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
435 440 445
Pro Gly Lys
450
<210> 446
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 人工序列的描述：合成多肽
<220>
<223> XENP31308链3- GCH065[GPC3] L0轻链
<400> 446
Asp Ile Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly
1 5 10 15
Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Pro Leu Val His Ser
20 25 30
Asn Arg Asn Thr Tyr Leu His Trp Tyr Gln Gln Lys Pro Gly Gln Ala
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gly Gln Gly
85 90 95
Thr Gln Val Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
Claims (52)
1.一种组合物，所述一组合物包含GPC3抗原结合结构域(ABD)，其中所述GPC3结合结构域包含来自选自由以下组成的组的可变重链结构域(VH)/可变轻链结构域(VL)对的一组6个CDR(vhCDR1、vhCDR2、vhCDR3、vlCDR1、vlCDR2和vlCDR3)：[GPC3]H1_L1、[GPC3]H1_L1.1、[GPC3]H1_L1.2、[GPC3]H1_L1.3、[GPC3]H1_L1.4、[GPC3]H1_L1.5、[GPC3]H1_L1.6、[GPC3]H1_L1.7、[GPC3]H1_L1.8、[GPC3]H1_L1.9、[GPC3]H1_L1.10、[GPC3]H1_L1.16、
[GPC3]H1_L1.23、[GPC3]H1_L1.29、[GPC3]H1_L1.31、
[GPC3]H1_L1.65、[GPC3]H1_L1.66、[GPC3]H1_L1.67、
[GPC3]H1_L1.68、[GPC3]H1_L1.70、[GPC3]H1_L1.71、
[GPC3]H1_L1.72、[GPC3]H1_L1.73、[GPC3]H1.1_L1、
[GPC3]H1.1_L1.1、[GPC3]H1.1_L1.2、[GPC3]H1.1_L1.3、
[GPC3]H1.1_L1.4、[GPC3]H1.1_L1.5、[GPC3]H1.1_L1.6、
[GPC3]H1.1_L1.7、[GPC3]H1.1_L1.8、[GPC3]H1.1_L1.9、
[GPC3]H1.1_L1.10、[GPC3]H1.1_L1.16、[GPC3]H1.1_L1.23、
[GPC3]H1.1_L1.29、[GPC3]H1.1_L1.31、[GPC3]H1.1_L1.65、
[GPC3]H1.1_L1.66、L1.67、[GPC3]H1.1_L1.68、[GPC3]H1.1_L1.70、[GPC3]H1.1_L1.71、[GPC3]H1.1_L1.72、[GPC3]H1.1_L1.73、
[GPC3]H1.2_L1、[GPC3]H1.2_L1.1、[GPC3]H1.2_L1.2、
[GPC3]H1.2_L1.3、[GPC3]H1.2_L1.4、[GPC3]H1.2_L1.5、
[GPC3]H1.2_L1.6、[GPC3]H1.2_L1.7、[GPC3]H1.2_L1.8、
[GPC3]H1.2_L1.9、[GPC3]H1.2_L1.10、[GPC3]H1.2_L1.16、
[GPC3]H1.2_L1.23、[GPC3]H1.2_L1.29、[GPC3]H1.2_L1.31、
[GPC3]H1.2_L1.65、[GPC3]H1.2_L1.66、[GPC3]H1.2_L1.67、
[GPC3]H1.2_L1.68、[GPC3]H1.2_L1.70、[GPC3]H1.2_L1.71、
[GPC3]H1.2_L1.72、[GPC3]H1.2_L1.73、[GPC3]H1.3_L1、
[GPC3]H1.3_L1.1、[GPC3]H1.3_L1.2、[GPC3]H1.3_L1.3、
[GPC3]H1.3_L1.4、[GPC3]H1.3_L1.5、[GPC3]H1.3_L1.6、
[GPC3]H1.3_L1.7、[GPC3]H1.3_L1.8、[GPC3]H1.3_L1.9、
[GPC3]H1.3_L1.10、[GPC3]H1.3_L1.16、[GPC3]H1.3_L1.23、
[GPC3]H1.3_L1.29、[GPC3]H1.3_L1.31、[GPC3]H1.3_L1.65、
[GPC3]H1.3_L1.66、[GPC3]H1.3_L1.67、[GPC3]H1.3_L1.68、
[GPC3]H1.3_L1.70、[GPC3]H1.3_L1.71、[GPC3]H1.3_L1.72、
[GPC3]H1.3_L1.73、[GPC3]H1.4_L1、[GPC3]H1.4_L1.1、
[GPC3]H1.4_L1.2、[GPC3]H1.4_L1.3、[GPC3]H1.4_L1.4、
[GPC3]H1.4_L1.5、[GPC3]H1.4_L1.6、[GPC3]H1.4_L1.7、
[GPC3]H1.4_L1.8、[GPC3]H1.4_L1.9、[GPC3]H1.4_L1.10、
[GPC3]H1.4_L1.16、[GPC3]H1.4_L1.23、[GPC3]H1.4_L1.29、
[GPC3]H1.4_L1.31、[GPC3]H1.4_L1.65、[GPC3]H1.4_L1.66、
[GPC3]H1.4_L1.67、[GPC3]H1.4_L1.68、[GPC3]H1.4_L1.70、
[GPC3]H1.4_L1.71、[GPC3]H1.4_L1.72和[GPC3]H1.4_L1.73。
2.根据权利要求1所述的组合物，其中所述ABD具有选自由以下组成的组的VH/VL对：[GPC3]H1_L1、[GPC3]H1_L1.1、[GPC3]H1_L1.2、[GPC3]H1_L1.3、[GPC3]H1_L1.4、[GPC3]H1_L1.5、[GPC3]H1_L1.6、[GPC3]H1_L1.7、[GPC3]H1_L1.8、[GPC3]H1_L1.9、
[GPC3]H1_L1.10、[GPC3]H1_L1.16、[GPC3]H1_L1.23、
[GPC3]H1_L1.29、[GPC3]H1_L1.31、[GPC3]H1_L1.65、
[GPC3]H1_L1.66、[GPC3]H1_L1.67、[GPC3]H1_L1.68、
[GPC3]H1_L1.70、[GPC3]H1_L1.71、[GPC3]H1_L1.72、
[GPC3]H1_L1.73、[GPC3]H1.1_L1、[GPC3]H1.1_L1.1、
[GPC3]H1.1_L1.2、[GPC3]H1.1_L1.3、[GPC3]H1.1_L1.4、
[GPC3]H1.1_L1.5、[GPC3]H1.1_L1.6、[GPC3]H1.1_L1.7、
[GPC3]H1.1_L1.8、[GPC3]H1.1_L1.9、[GPC3]H1.1_L1.10、
[GPC3]H1.1_L1.16、[GPC3]H1.1_L1.23、[GPC3]H1.1_L1.29、
[GPC3]H1.1_L1.31、[GPC3]H1.1_L1.65、[GPC3]H1.1_L1.66、L1.67、[GPC3]H1.1_L1.68、[GPC3]H1.1_L1.70、[GPC3]H1.1_L1.71、
[GPC3]H1.1_L1.72、[GPC3]H1.1_L1.73、[GPC3]H1.2_L1、
[GPC3]H1.2_L1.1、[GPC3]H1.2_L1.2、[GPC3]H1.2_L1.3、
[GPC3]H1.2_L1.4、[GPC3]H1.2_L1.5、[GPC3]H1.2_L1.6、
[GPC3]H1.2_L1.7、[GPC3]H1.2_L1.8、[GPC3]H1.2_L1.9、
[GPC3]H1.2_L1.10、[GPC3]H1.2_L1.16、[GPC3]H1.2_L1.23、
[GPC3]H1.2_L1.29、[GPC3]H1.2_L1.31、[GPC3]H1.2_L1.65、
[GPC3]H1.2_L1.66、[GPC3]H1.2_L1.67、[GPC3]H1.2_L1.68、
[GPC3]H1.2_L1.70、[GPC3]H1.2_L1.71、[GPC3]H1.2_L1.72、
[GPC3]H1.2_L1.73、[GPC3]H1.3_L1、[GPC3]H1.3_L1.1、
[GPC3]H1.3_L1.2、[GPC3]H1.3_L1.3、[GPC3]H1.3_L1.4、
[GPC3]H1.3_L1.5、[GPC3]H1.3_L1.6、[GPC3]H1.3_L1.7、
[GPC3]H1.3_L1.8、[GPC3]H1.3_L1.9、[GPC3]H1.3_L1.10、
[GPC3]H1.3_L1.16、[GPC3]H1.3_L1.23、[GPC3]H1.3_L1.29、
[GPC3]H1.3_L1.31、[GPC3]H1.3_L1.65、[GPC3]H1.3_L1.66、
[GPC3]H1.3_L1.67、[GPC3]H1.3_L1.68、[GPC3]H1.3_L1.70、
[GPC3]H1.3_L1.71、[GPC3]H1.3_L1.72、[GPC3]H1.3_L1.73、
[GPC3]H1.4_L1、[GPC3]H1.4_L1.1、[GPC3]H1.4_L1.2、
[GPC3]H1.4_L1.3、[GPC3]H1.4_L1.4、[GPC3]H1.4_L1.5、
[GPC3]H1.4_L1.6、[GPC3]H1.4_L1.7、[GPC3]H1.4_L1.8、
[GPC3]H1.4_L1.9、[GPC3]H1.4_L1.10、[GPC3]H1.4_L1.16、
[GPC3]H1.4_L1.23、[GPC3]H1.4_L1.29、[GPC3]H1.4_L1.31、
[GPC3]H1.4_L1.65、[GPC3]H1.4_L1.66、[GPC3]H1.4_L1.67、
[GPC3]H1.4_L1.68、[GPC3]H1.4_L1.70、[GPC3]H1.4_L1.71、
[GPC3]H1.4_L1.72和[GPC3]H1.4_L1.73。
3.根据权利要求2所述的组合物，其中所述VH/VL对选自由[GPC3]H1.1_L1.16和[GPC3]H1.1_L1.69组成的组。
4.根据权利要求1至3中任一项所述的组合物，其中所述一组合物是单克隆抗体。
5.一种核酸组合物，所述核酸组合物包含：
a)第一核酸，所述第一核酸编码VH结构域；和
b)第二核酸，所述第二核酸编码VL结构域，其中所述VH和所述VL是选自由以下组成的组的对：[GPC3]H1_L1、
[GPC3]H1_L1.1、[GPC3]H1_L1.2、[GPC3]H1_L1.3、
[GPC3]H1_L1.4、[GPC3]H1_L1.5、[GPC3]H1_L1.6、[GPC3]H1_L1.7、[GPC3]H1_L1.8、[GPC3]H1_L1.9、[GPC3]H1_L1.10、[GPC3]H1_L1.16、[GPC3]H1_L1.23、[GPC3]H1_L1.29、[GPC3]H1_L1.31、[GPC3]H1_L1.65、[GPC3]H1_L1.66、[GPC3]H1_L1.67、[GPC3]H1_L1.68、[GPC3]H1_L1.70、[GPC3]H1_L1.71、[GPC3]H1_L1.72、[GPC3]H1_L1.73、[GPC3]H1.1_L1、[GPC3]H1.1_L1.1、[GPC3]H1.1_L1.2、[GPC3]H1.1_L1.3、[GPC3]H1.1_L1.4、[GPC3]H1.1_L1.5、[GPC3]H1.1_L1.6、[GPC3]H1.1_L1.7、[GPC3]H1.1_L1.8、[GPC3]H1.1_L1.9、[GPC3]H1.1_L1.10、[GPC3]H1.1_L1.16、[GPC3]H1.1_L1.23、[GPC3]H1.1_L1.29、[GPC3]H1.1_L1.31、[GPC3]H1.1_L1.65、[GPC3]H1.1_L1.66、L1.67、[GPC3]H1.1_L1.68、[GPC3]H1.1_L1.70、[GPC3]H1.1_L1.71、[GPC3]H1.1_L1.72、[GPC3]H1.1_L1.73、[GPC3]H1.2_L1、[GPC3]H1.2_L1.1、[GPC3]H1.2_L1.2、[GPC3]H1.2_L1.3、[GPC3]H1.2_L1.4、[GPC3]H1.2_L1.5、[GPC3]H1.2_L1.6、[GPC3]H1.2_L1.7、[GPC3]H1.2_L1.8、[GPC3]H1.2_L1.9、[GPC3]H1.2_L1.10、[GPC3]H1.2_L1.16、[GPC3]H1.2_L1.23、[GPC3]H1.2_L1.29、[GPC3]H1.2_L1.31、[GPC3]H1.2_L1.65、[GPC3]H1.2_L1.66、[GPC3]H1.2_L1.67、[GPC3]H1.2_L1.68、[GPC3]H1.2_L1.70、[GPC3]H1.2_L1.71、[GPC3]H1.2_L1.72、[GPC3]H1.2_L1.73、[GPC3]H1.3_L1、[GPC3]H1.3_L1.1、[GPC3]H1.3_L1.2、[GPC3]H1.3_L1.3、[GPC3]H1.3_L1.4、[GPC3]H1.3_L1.5、[GPC3]H1.3_L1.6、[GPC3]H1.3_L1.7、[GPC3]H1.3_L1.8、[GPC3]H1.3_L1.9、[GPC3]H1.3_L1.10、[GPC3]H1.3_L1.16、[GPC3]H1.3_L1.23、[GPC3]H1.3_L1.29、[GPC3]H1.3_L1.31、[GPC3]H1.3_L1.65、[GPC3]H1.3_L1.66、[GPC3]H1.3_L1.67、[GPC3]H1.3_L1.68、[GPC3]H1.3_L1.70、[GPC3]H1.3_L1.71、[GPC3]H1.3_L1.72、[GPC3]H1.3_L1.73、[GPC3]H1.4_L1、[GPC3]H1.4_L1.1、[GPC3]H1.4_L1.2、[GPC3]H1.4_L1.3、[GPC3]H1.4_L1.4、[GPC3]H1.4_L1.5、[GPC3]H1.4_L1.6、[GPC3]H1.4_L1.7、[GPC3]H1.4_L1.8、[GPC3]H1.4_L1.9、[GPC3]H1.4_L1.10、
[GPC3]H1.4_L1.16、[GPC3]H1.4_L1.23、[GPC3]H1.4_L1.29、
[GPC3]H1.4_L1.31、[GPC3]H1.4_L1.65、[GPC3]H1.4_L1.66、
[GPC3]H1.4_L1.67、[GPC3]H1.4_L1.68、[GPC3]H1.4_L1.70、
[GPC3]H1.4_L1.71、[GPC3]H1.4_L1.72和[GPC3]H1.4_L1.73。
6.一种表达载体组合物，所述表达载体组合物分别包含：
a)第一表达载体，所述第一表达载体包含根据权利要求5所述的第一核酸；和
b)第二表达载体，所述第二表达载体包含根据权利要求5所述的第二核酸。
7.一种表达载体，所述表达载体包含根据权利要求5所述的第一核酸和所述第二核酸。
8.一种宿主细胞，所述宿主细胞包含根据权利要求6所述的表达载体组合物或根据权利要求7所述的表达载体。
9.一种制备抗GPC3 ABD的方法，所述方法包括在表达所述ABD的条件下培养根据权利要求8所述的宿主细胞，以及回收所述ABD。
10.一种异二聚抗体，所述异二聚抗体包含：
a)第一单体，所述第一单体包含：
i)抗CD3 scFv，所述抗CD3 scFv包含第一可变轻链结构域、scFv接头和第一可变重链结构域；和
ii)第一Fc结构域，其中所述scFv使用结构域接头共价附接至所述第一Fc结构域的N末端；
b)第二单体，所述第二单体包含VH2-CH1-铰链-CH2-CH3单体，其中VH是第二可变重链结构域，并且CH2-CH3是第二Fc结构域；和
c)轻链，所述轻链包含第二可变轻链结构域，
其中所述第二可变重链结构域和所述第二可变轻链结构域形成GPC3抗原结合结构域(ABD)。
11.根据权利要求10所述的异二聚抗体，其中所述GPC3结合结构域包含来自选自由以下组成的组的VH/VL对的一组6个CDR(vhCDR1、vhCDR2、vhCDR3、vlCDR1、vlCDR2和vlCDR3)：[GPC3]H1_L1、[GPC3]H1_L1.1、[GPC3]H1_L1.2、[GPC3]H1_L1.3、[GPC3]H1_L1.4、[GPC3]H1_L1.5、[GPC3]H1_L1.6、[GPC3]H1_L1.7、[GPC3]H1_L1.8、[GPC3]H1_L1.9、[GPC3]H1_L1.10、[GPC3]H1_L1.16、[GPC3]H1_L1.23、[GPC3]H1_L1.29、[GPC3]H1_L1.31、[GPC3]H1_L1.65、[GPC3]H1_L1.66、[GPC3]H1_L1.67、[GPC3]H1_L1.68、[GPC3]H1_L1.70、[GPC3]H1_L1.71、[GPC3]H1_L1.72、[GPC3]H1_L1.73、[GPC3]H1.1_L1、[GPC3]H1.1_L1.1、[GPC3]H1.1_L1.2、[GPC3]H1.1_L1.3、[GPC3]H1.1_L1.4、[GPC3]H1.1_L1.5、[GPC3]H1.1_L1.6、[GPC3]H1.1_L1.7、[GPC3]H1.1_L1.8、[GPC3]H1.1_L1.9、[GPC3]H1.1_L1.10、[GPC3]H1.1_L1.16、[GPC3]H1.1_L1.23、[GPC3]H1.1_L1.29、[GPC3]H1.1_L1.31、[GPC3]H1.1_L1.65、[GPC3]H1.1_L1.66、L1.67、[GPC3]H1.1_L1.68、[GPC3]H1.1_L1.70、[GPC3]H1.1_L1.71、[GPC3]H1.1_L1.72、[GPC3]H1.1_L1.73、[GPC3]H1.2_L1、[GPC3]H1.2_L1.1、[GPC3]H1.2_L1.2、[GPC3]H1.2_L1.3、[GPC3]H1.2_L1.4、[GPC3]H1.2_L1.5、[GPC3]H1.2_L1.6、[GPC3]H1.2_L1.7、[GPC3]H1.2_L1.8、[GPC3]H1.2_L1.9、[GPC3]H1.2_L1.10、[GPC3]H1.2_L1.16、[GPC3]H1.2_L1.23、[GPC3]H1.2_L1.29、[GPC3]H1.2_L1.31、[GPC3]H1.2_L1.65、[GPC3]H1.2_L1.66、[GPC3]H1.2_L1.67、[GPC3]H1.2_L1.68、[GPC3]H1.2_L1.70、[GPC3]H1.2_L1.71、[GPC3]H1.2_L1.72、[GPC3]H1.2_L1.73、[GPC3]H1.3_L1、[GPC3]H1.3_L1.1、[GPC3]H1.3_L1.2、[GPC3]H1.3_L1.3、[GPC3]H1.3_L1.4、[GPC3]H1.3_L1.5、[GPC3]H1.3_L1.6、[GPC3]H1.3_L1.7、[GPC3]H1.3_L1.8、[GPC3]H1.3_L1.9、[GPC3]H1.3_L1.10、[GPC3]H1.3_L1.16、[GPC3]H1.3_L1.23、[GPC3]H1.3_L1.29、[GPC3]H1.3_L1.31、[GPC3]H1.3_L1.65、[GPC3]H1.3_L1.66、[GPC3]H1.3_L1.67、[GPC3]H1.3_L1.68、[GPC3]H1.3_L1.70、[GPC3]H1.3_L1.71、[GPC3]H1.3_L1.72、[GPC3]H1.3_L1.73、[GPC3]H1.4_L1、[GPC3]H1.4_L1.1、[GPC3]H1.4_L1.2、[GPC3]H1.4_L1.3、[GPC3]H1.4_L1.4、
[GPC3]H1.4_L1.5、[GPC3]H1.4_L1.6、[GPC3]H1.4_L1.7、
[GPC3]H1.4_L1.8、[GPC3]H1.4_L1.9、[GPC3]H1.4_L1.10、
[GPC3]H1.4_L1.16、[GPC3]H1.4_L1.23、[GPC3]H1.4_L1.29、
[GPC3]H1.4_L1.31、[GPC3]H1.4_L1.65、[GPC3]H1.4_L1.66、
[GPC3]H1.4_L1.67、[GPC3]H1.4_L1.68、[GPC3]H1.4_L1.70、
[GPC3]H1.4_L1.71、[GPC3]H1.4_L1.72和[GPC3]H1.4_L1.73。
12.根据权利要求10或11所述的异二聚抗体，其中所述GPC3结合结构域包含选自由以下组成的组的VH/VL对：[GPC3]H1_L1、
[GPC3]H1_L1.1、[GPC3]H1_L1.2、[GPC3]H1_L1.3、[GPC3]H1_L1.4、[GPC3]H1_L1.5、[GPC3]H1_L1.6、[GPC3]H1_L1.7、[GPC3]H1_L1.8、[GPC3]H1_L1.9、[GPC3]H1_L1.10、[GPC3]H1_L1.16、
[GPC3]H1_L1.23、[GPC3]H1_L1.29、[GPC3]H1_L1.31、
[GPC3]H1_L1.65、[GPC3]H1_L1.66、[GPC3]H1_L1.67、
[GPC3]H1_L1.68、[GPC3]H1_L1.70、[GPC3]H1_L1.71、
[GPC3]H1_L1.72、[GPC3]H1_L1.73、[GPC3]H1.1_L1、
[GPC3]H1.1_L1.1、[GPC3]H1.1_L1.2、[GPC3]H1.1_L1.3、
[GPC3]H1.1_L1.4、[GPC3]H1.1_L1.5、[GPC3]H1.1_L1.6、
[GPC3]H1.1_L1.7、[GPC3]H1.1_L1.8、[GPC3]H1.1_L1.9、
[GPC3]H1.1_L1.10、[GPC3]H1.1_L1.16、[GPC3]H1.1_L1.23、
[GPC3]H1.1_L1.29、[GPC3]H1.1_L1.31、[GPC3]H1.1_L1.65、
[GPC3]H1.1_L1.66、L1.67、[GPC3]H1.1_L1.68、[GPC3]H1.1_L1.70、[GPC3]H1.1_L1.71、[GPC3]H1.1_L1.72、[GPC3]H1.1_L1.73、
[GPC3]H1.2_L1、[GPC3]H1.2_L1.1、[GPC3]H1.2_L1.2、
[GPC3]H1.2_L1.3、[GPC3]H1.2_L1.4、[GPC3]H1.2_L1.5、
[GPC3]H1.2_L1.6、[GPC3]H1.2_L1.7、[GPC3]H1.2_L1.8、
[GPC3]H1.2_L1.9、[GPC3]H1.2_L1.10、[GPC3]H1.2_L1.16、
[GPC3]H1.2_L1.23、[GPC3]H1.2_L1.29、[GPC3]H1.2_L1.31、
[GPC3]H1.2_L1.65、[GPC3]H1.2_L1.66、[GPC3]H1.2_L1.67、
[GPC3]H1.2_L1.68、[GPC3]H1.2_L1.70、[GPC3]H1.2_L1.71、
[GPC3]H1.2_L1.72、[GPC3]H1.2_L1.73、[GPC3]H1.3_L1、
[GPC3]H1.3_L1.1、[GPC3]H1.3_L1.2、[GPC3]H1.3_L1.3、
[GPC3]H1.3_L1.4、[GPC3]H1.3_L1.5、[GPC3]H1.3_L1.6、
[GPC3]H1.3_L1.7、[GPC3]H1.3_L1.8、[GPC3]H1.3_L1.9、
[GPC3]H1.3_L1.10、[GPC3]H1.3_L1.16、[GPC3]H1.3_L1.23、
[GPC3]H1.3_L1.29、[GPC3]H1.3_L1.31、[GPC3]H1.3_L1.65、
[GPC3]H1.3_L1.66、[GPC3]H1.3_L1.67、[GPC3]H1.3_L1.68、
[GPC3]H1.3_L1.70、[GPC3]H1.3_L1.71、[GPC3]H1.3_L1.72、
[GPC3]H1.3_L1.73、[GPC3]H1.4_L1、[GPC3]H1.4_L1.1、
[GPC3]H1.4_L1.2、[GPC3]H1.4_L1.3、[GPC3]H1.4_L1.4、
[GPC3]H1.4_L1.5、[GPC3]H1.4_L1.6、[GPC3]H1.4_L1.7、
[GPC3]H1.4_L1.8、[GPC3]H1.4_L1.9、[GPC3]H1.4_L1.10、
[GPC3]H1.4_L1.16、[GPC3]H1.4_L1.23、[GPC3]H1.4_L1.29、
[GPC3]H1.4_L1.31、[GPC3]H1.4_L1.65、[GPC3]H1.4_L1.66、
[GPC3]H1.4_L1.67、[GPC3]H1.4_L1.68、[GPC3]H1.4_L1.70、
[GPC3]H1.4_L1.71、[GPC3]H1.4_L1.72和[GPC3]H1.4_L1.73。
13.根据权利要求10或11所述的异二聚抗体，其中所述GPC3结合结构域包含选自由以下组成的组的VH/VL对：[GPC3]H1.1_L1.16和[GPC3]H1.1_L1.69。
14.根据权利要求10至13中任一项所述的异二聚抗体，其中所述抗CD3scFv包含选自由以下组成的组的VH和VL对：H1.30_L1.47、H1.32_L1.47、H1.89_L1.47、H1.90_L1.47、H1.33_L1.47、H1.31_L1.47、L1.47_H1.30、L1.47_H1.30、L1.47_H1.32、L1.47_H1.89、L1.47_H1.90、L1.47_H1.33和L1.47_H1.31。
15.根据权利要求10至15中任一项所述的异二聚抗体，其中所述scFv接头是带电荷的scFv接头。
16.根据权利要求10至16中任一项所述的异二聚抗体，其中所述第一Fc结构域和所述第二Fc结构域是变体Fc结构域。
17.根据权利要求16中任一项所述的异二聚抗体，其中所述第一单体和所述第二单体包含选自由图1A至图1E中所描绘的异二聚化变体组成的组的一组异二聚化变体。
18.根据权利要求17所述的异二聚抗体，其中所述一组异二聚化变体选自由以下组成的组：S364K/E357Q:L368D/K370S；
S364K:L368D/K370S；S364K:L368E/K370S；D401K:T411E/K360E/Q362E；和T366W:T366S/L368A/Y407V，其中编号是根据EU编号进行的。
19.根据权利要求17或18所述的异二聚抗体，其中所述第一单体和所述第二单体还包含一种或多种消融变体。
20.根据权利要求19所述的异二聚抗体，其中所述一种或多种消融变体是E233P/L234V/L235A/G236del/S267K，其中编号是根据EU编号进行的。
21.根据权利要求10至20中任一项所述的异二聚抗体，其中所述第一单体或所述第二单体中的一者包含一种或多种pI变体。
22.根据权利要求21所述的异二聚抗体，其中所述pI变体是N208D/Q295E/N384D/Q418E/N421D，其中编号是根据EU编号进行的。
23.根据权利要求10至22中任一项所述的异二聚抗体，其中所述第一单体包含氨基酸变体S364K/E357Q/E233P/L234V/L235A/G236del/S267K，
其中所述第二单体包含氨基酸变体L368D/K370S/N208D/Q295E/N384D/Q418E/N421D/E233P/L234V/L235A/G236del/S267K，并且
其中编号是根据EU编号进行的。
24.根据权利要求23所述的异二聚抗体，其中所述第一单体和所述第二单体各自还包含氨基酸变体428/434S。
25.一种异二聚抗体，所述异二聚抗体包含：
a)第一单体，所述第一单体从N末端到C末端包含scFv-接头-CH2-CH3，
其中scFv是抗CD3 scFv，并且CH2-CH3是第一Fc结构域；
b)第二单体，所述第二单体从N末端到C末端包含VH-CH1-铰链-CH2-CH3，其中CH2-CH3是第二Fc结构域；和
c)轻链，所述轻链包含VL-CL；
其中所述第一变体Fc结构域包含氨基酸变体S364K/E357Q，
其中所述第二变体Fc结构域包含氨基酸变体L368D/K370S，其中所述第一变体Fc结构域和所述第二变体Fc结构域各自包含氨基酸变体E233P/L234V/L235A/G236del/S267K，
其中所述第二单体的CH1-铰链-CH2-CH3包含氨基酸变体N208D/Q295E/N384D/Q418E/N421D，
其中所述VH和所述VL形成分别包含选自[GPC3]H1.1_L1.16的GPC3结合结构域的可变重链结构域和[GPC3]H1.1_L1.69的GPC3结合结构域的可变轻链结构域，
其中所述抗CD3 scFv包含选自以下的CD3结合结构域的可变重链结构域和可变轻链结构域：H1.30_L1.47、H1.32_L1.47、H1.89_L1.47、H1.90_L1.47、H1.33_L1.47、H1.31_L1.47、L1.47_H1.30、L1.47_H1.30、L1.47_H1.32、L1.47_H1.89、L1.47_H1.90、L1.47_H1.33和L1.47_H1.31，并且
其中编号是根据EU编号进行的。
26.根据权利要求25所述的异二聚抗体，其中所述第一变体Fc结构域和所述第二变体Fc结构域各自还包含氨基酸变体428/434S，其中编号是根据EU编号进行的。
27.一种核酸组合物，所述核酸组合物分别包含：
a)第一核酸，所述第一核酸编码根据权利要求10至26中任一项所述的第一单体；
b)第二核酸，所述第二核酸编码根据权利要求10至26中任一项所述的第二单体；和
c)第三核酸，所述第三核酸编码根据权利要求10至26中任一项所述的轻链。
28.一种表达载体组合物，所述表达载体组合物包含：
a)第一表达载体，所述第一表达载体包含根据权利要求26所述的第一核酸；
b)第二表达载体，所述第二表达载体包含根据权利要求26所述的第二核酸；和
c)第三表达载体，所述第三表达载体包含根据权利要求26所述的第三核酸。
29.一种宿主细胞，所述宿主细胞用根据权利要求28所述的表达载体组合物转化。
30.一种制备异二聚抗体的方法，所述方法包括在表达所述抗体的条件下培养根据权利要求29所述的宿主细胞，以及回收所述抗体。
31.一种异二聚抗体，所述异二聚抗体包含：
a)第一单体，所述第一单体从N末端到C末端包含VH1-CH1-接头1-scFv-接头2-CH2-CH3，
其中VH1是第一可变重链结构域，scFv是抗CD3 scFv，接头1和接头2分别是第一结构域接头和第二结构域接头，并且CH2-CH3是第一Fc结构域；
b)第二单体，所述第二单体从N末端到C末端包含VH2-CH1-铰链-CH2-CH3，其中VH2是第二可变重链结构域，并且CH2-CH3是第二Fc结构域；和
c)共同轻链，所述共同轻链包含可变轻链结构域；
其中所述第一可变重链结构域和所述可变轻链结构域形成第一GPC3ABD，并且所述第二可变重链结构域和所述可变轻链结构域形成第二GPC3 ABD。
32.根据权利要求31所述的异二聚抗体，其中所述第一GPC3结合结构域和所述第二GPC3结合结构域各自包含来自选自由以下组成的组的VH/VL对的一组6个CDR(vhCDR1、vhCDR2、vhCDR3、vlCDR1、vlCDR2和vlCDR3)：[GPC3]H1_L1、[GPC3]H1_L1.1、
[GPC3]H1_L1.2、[GPC3]H1_L1.3、[GPC3]H1_L1.4、[GPC3]H1_L1.5、[GPC3]H1_L1.6、[GPC3]H1_L1.7、[GPC3]H1_L1.8、[GPC3]H1_L1.9、[GPC3]H1_L1.10、[GPC3]H1_L1.16、[GPC3]H1_L1.23、
[GPC3]H1_L1.29、[GPC3]H1_L1.31、[GPC3]H1_L1.65、
[GPC3]H1_L1.66、[GPC3]H1_L1.67、[GPC3]H1_L1.68、
[GPC3]H1_L1.70、[GPC3]H1_L1.71、[GPC3]H1_L1.72、
[GPC3]H1_L1.73、[GPC3]H1.1_L1、[GPC3]H1.1_L1.1、
[GPC3]H1.1_L1.2、[GPC3]H1.1_L1.3、[GPC3]H1.1_L1.4、
[GPC3]H1.1_L1.5、[GPC3]H1.1_L1.6、[GPC3]H1.1_L1.7、
[GPC3]H1.1_L1.8、[GPC3]H1.1_L1.9、[GPC3]H1.1_L1.10、
[GPC3]H1.1_L1.16、[GPC3]H1.1_L1.23、[GPC3]H1.1_L1.29、
[GPC3]H1.1_L1.31、[GPC3]H1.1_L1.65、[GPC3]H1.1_L1.66、L1.67、[GPC3]H1.1_L1.68、[GPC3]H1.1_L1.70、[GPC3]H1.1_L1.71、
[GPC3]H1.1_L1.72、[GPC3]H1.1_L1.73、[GPC3]H1.2_L1、
[GPC3]H1.2_L1.1、[GPC3]H1.2_L1.2、[GPC3]H1.2_L1.3、
[GPC3]H1.2_L1.4、[GPC3]H1.2_L1.5、[GPC3]H1.2_L1.6、
[GPC3]H1.2_L1.7、[GPC3]H1.2_L1.8、[GPC3]H1.2_L1.9、
[GPC3]H1.2_L1.10、[GPC3]H1.2_L1.16、[GPC3]H1.2_L1.23、
[GPC3]H1.2_L1.29、[GPC3]H1.2_L1.31、[GPC3]H1.2_L1.65、
[GPC3]H1.2_L1.66、[GPC3]H1.2_L1.67、[GPC3]H1.2_L1.68、
[GPC3]H1.2_L1.70、[GPC3]H1.2_L1.71、[GPC3]H1.2_L1.72、
[GPC3]H1.2_L1.73、[GPC3]H1.3_L1、[GPC3]H1.3_L1.1、
[GPC3]H1.3_L1.2、[GPC3]H1.3_L1.3、[GPC3]H1.3_L1.4、
[GPC3]H1.3_L1.5、[GPC3]H1.3_L1.6、[GPC3]H1.3_L1.7、
[GPC3]H1.3_L1.8、[GPC3]H1.3_L1.9、[GPC3]H1.3_L1.10、
[GPC3]H1.3_L1.16、[GPC3]H1.3_L1.23、[GPC3]H1.3_L1.29、
[GPC3]H1.3_L1.31、[GPC3]H1.3_L1.65、[GPC3]H1.3_L1.66、
[GPC3]H1.3_L1.67、[GPC3]H1.3_L1.68、[GPC3]H1.3_L1.70、
[GPC3]H1.3_L1.71、[GPC3]H1.3_L1.72、[GPC3]H1.3_L1.73、
[GPC3]H1.4_L1、[GPC3]H1.4_L1.1、[GPC3]H1.4_L1.2、
[GPC3]H1.4_L1.3、[GPC3]H1.4_L1.4、[GPC3]H1.4_L1.5、
[GPC3]H1.4_L1.6、[GPC3]H1.4_L1.7、[GPC3]H1.4_L1.8、
[GPC3]H1.4_L1.9、[GPC3]H1.4_L1.10、[GPC3]H1.4_L1.16、
[GPC3]H1.4_L1.23、[GPC3]H1.4_L1.29、[GPC3]H1.4_L1.31、
[GPC3]H1.4_L1.65、[GPC3]H1.4_L1.66、[GPC3]H1.4_L1.67、
[GPC3]H1.4_L1.68、[GPC3]H1.4_L1.70、[GPC3]H1.4_L1.71、
[GPC3]H1.4_L1.72和[GPC3]H1.4_L1.73。
33.根据权利要求31至32所述的异二聚抗体，其中所述第一GPC3结合结构域和所述第二GPC3结合结构域中的每一者具有选自由以下组成的组的VH/VL对：[GPC3]H1_L1、[GPC3]H1_L1.1、[GPC3]H1_L1.2、[GPC3]H1_L1.3、[GPC3]H1_L1.4、[GPC3]H1_L1.5、[GPC3]H1_L1.6、[GPC3]H1_L1.7、[GPC3]H1_L1.8、[GPC3]H1_L1.9、[GPC3]H1_L1.10、[GPC3]H1_L1.16、[GPC3]H1_L1.23、[GPC3]H1_L1.29、[GPC3]H1_L1.31、[GPC3]H1_L1.65、[GPC3]H1_L1.66、[GPC3]H1_L1.67、[GPC3]H1_L1.68、[GPC3]H1_L1.70、[GPC3]H1_L1.71、[GPC3]H1_L1.72、[GPC3]H1_L1.73、[GPC3]H1.1_L1、[GPC3]H1.1_L1.1、[GPC3]H1.1_L1.2、[GPC3]H1.1_L1.3、[GPC3]H1.1_L1.4、[GPC3]H1.1_L1.5、[GPC3]H1.1_L1.6、[GPC3]H1.1_L1.7、[GPC3]H1.1_L1.8、[GPC3]H1.1_L1.9、[GPC3]H1.1_L1.10、[GPC3]H1.1_L1.16、[GPC3]H1.1_L1.23、[GPC3]H1.1_L1.29、[GPC3]H1.1_L1.31、[GPC3]H1.1_L1.65、[GPC3]H1.1_L1.66、L1.67、[GPC3]H1.1_L1.68、[GPC3]H1.1_L1.70、[GPC3]H1.1_L1.71、[GPC3]H1.1_L1.72、[GPC3]H1.1_L1.73、[GPC3]H1.2_L1、[GPC3]H1.2_L1.1、[GPC3]H1.2_L1.2、[GPC3]H1.2_L1.3、[GPC3]H1.2_L1.4、[GPC3]H1.2_L1.5、[GPC3]H1.2_L1.6、[GPC3]H1.2_L1.7、[GPC3]H1.2_L1.8、[GPC3]H1.2_L1.9、[GPC3]H1.2_L1.10、[GPC3]H1.2_L1.16、[GPC3]H1.2_L1.23、[GPC3]H1.2_L1.29、[GPC3]H1.2_L1.31、[GPC3]H1.2_L1.65、[GPC3]H1.2_L1.66、[GPC3]H1.2_L1.67、[GPC3]H1.2_L1.68、[GPC3]H1.2_L1.70、[GPC3]H1.2_L1.71、[GPC3]H1.2_L1.72、[GPC3]H1.2_L1.73、[GPC3]H1.3_L1、[GPC3]H1.3_L1.1、[GPC3]H1.3_L1.2、[GPC3]H1.3_L1.3、[GPC3]H1.3_L1.4、[GPC3]H1.3_L1.5、[GPC3]H1.3_L1.6、[GPC3]H1.3_L1.7、[GPC3]H1.3_L1.8、[GPC3]H1.3_L1.9、[GPC3]H1.3_L1.10、[GPC3]H1.3_L1.16、[GPC3]H1.3_L1.23、[GPC3]H1.3_L1.29、[GPC3]H1.3_L1.31、[GPC3]H1.3_L1.65、[GPC3]H1.3_L1.66、[GPC3]H1.3_L1.67、[GPC3]H1.3_L1.68、[GPC3]H1.3_L1.70、[GPC3]H1.3_L1.71、[GPC3]H1.3_L1.72、[GPC3]H1.3_L1.73、[GPC3]H1.4_L1、[GPC3]H1.4_L1.1、[GPC3]H1.4_L1.2、[GPC3]H1.4_L1.3、[GPC3]H1.4_L1.4、[GPC3]H1.4_L1.5、[GPC3]H1.4_L1.6、[GPC3]H1.4_L1.7、[GPC3]H1.4_L1.8、
[GPC3]H1.4_L1.9、[GPC3]H1.4_L1.10、[GPC3]H1.4_L1.16、
[GPC3]H1.4_L1.23、[GPC3]H1.4_L1.29、[GPC3]H1.4_L1.31、
[GPC3]H1.4_L1.65、[GPC3]H1.4_L1.66、[GPC3]H1.4_L1.67、
[GPC3]H1.4_L1.68、[GPC3]H1.4_L1.70、[GPC3]H1.4_L1.71、
[GPC3]H1.4_L1.72和[GPC3]H1.4_L1.73。
34.根据权利要求31至33中任一项所述的异二聚抗体，其中所述VH/VL对选自由[GPC3]H1.1_L1.16和[GPC3]H1.1_L1.69组成的组。
35.根据权利要求31至35中任一项所述的异二聚抗体，其中所述scFv包含具有来自选自由以下组成的组的VH/VL对的一组6个CDR(vhCDR1、vhCDR2、vhCDR3、vlCDR1、vlCDR2和vlCDR3)：
H1.30_L1.47、H1.32_L1.47、H1.89_L1.47、H1.90_L1.47、H1.33_L1.47、H1.31_L1.47、L1.47_H1.30、L1.47_H1.30、L1.47_H1.32、L1.47_H1.89、L1.47_H1.90、L1.47_H1.33和L1.47_H1.31。
36.根据权利要求35所述的异二聚抗体，其中所述scFv包含以下CD3结合结构域中的任一者的所述可变重链结构域和所述可变轻链结构域：H1.30_L1.47、H1.32_L1.47、H1.89_L1.47、H1.90_L1.47、H1.33_L1.47、H1.31_L1.47、L1.47_H1.30、L1.47_H1.30、L1.47_H1.32、L1.47_H1.89、L1.47_H1.90、L1.47_H1.33和L1.47_H1.31。
37.根据权利要求31至36中任一项所述的异二聚抗体，其中所述第一Fc结构域和所述第二Fc结构域是变体Fc结构域。
38.根据权利要求31至37中任一项所述的异二聚抗体，其中所述第一单体和所述第二单体包含选自由图1A至图1E中所描绘的异二聚化变体组成的组的一组异二聚化变体。
39.根据权利要求38所述的异二聚抗体，其中所述一组异二聚化变体选自由以下组成的组：S364K/E357Q:L368D/K370S；
S364K:L368D/K370S；S364K:L368E/K370S；D401K:T411E/K360E/Q362E；和T366W:T366S/L368A/Y407V，其中编号是根据EU编号进行的。
40.根据权利要求31至39中任一项所述的异二聚抗体，其中所述第一单体和所述第二单体还包含一种或多种消融变体。
41.根据权利要求40所述的异二聚抗体，其中所述一种或多种消融变体是E233P/L234V/L235A/G236del/S267K，其中编号是根据EU编号进行的。
42.根据权利要求31至41中任一项所述的异二聚抗体，其中所述第一单体或所述第二单体中的一者还包含一种或多种pI变体。
43.根据权利要求42所述的异二聚抗体，其中所述pI变体是N208D/Q295E/N384D/Q418E/N421D，其中编号是根据EU编号进行的。
44.根据权利要求31至43中任一项所述的异二聚抗体，其中所述第一变体Fc结构域包含氨基酸变体S364K/E357Q/E233P/L234V/L235A/G236del/S267K，
其中所述第二变体Fc结构域包含氨基酸变体L368D/K370S/N208D/Q295E/N384D/Q418E/N421D/E233P/L234V/L235A/G236del/S267K，并且其中编号是根据EU编号进行的。
45.根据权利要求44所述的异二聚抗体，其中所述scFv接头是具有氨基酸序列(GKPGS)4(SEQ ID NO:15)的带电荷的scFv接头。
46.根据权利要求45所述的异二聚抗体，其中所述第一变体Fc结构域和所述第二变体Fc结构域各自还包含氨基酸变体428/434S，其中编号是根据EU编号进行的。
47.一种异二聚抗体，所述异二聚抗体包含：
a)第一单体，所述第一单体从N末端到C末端包含VH1-CH1-接头1-scFv-接头2-CH2-CH3，
其中scFv是抗CD3 scFv，并且CH2-CH3是第一Fc结构域；
b)第二单体，所述第二单体从N末端到C末端包含VH1-CH1-铰链-CH2-CH3，其中CH2-CH3是第二Fc结构域；和
c)共同轻链，所述共同轻链包含VL-CL；
其中所述第一变体Fc结构域包含氨基酸变体S364K/E357Q，
其中所述第二变体Fc结构域包含氨基酸变体L368D/K370S，其中所述第一变体Fc结构域和所述第二变体Fc结构域各自包含氨基酸变体E233P/L234V/L235A/G236del/S267K，
其中所述第二单体的CH1-铰链-CH2-CH3包含氨基酸变体N208D/Q295E/N384D/Q418E/N421D，
其中所述VH和所述VL包含选自以下的GPC3 ABD的可变重链结构域和可变轻链结构域：H1.9_L1.187、H1.24_L1.187、H2.91_L1.187和H1.9_L1.187；
其中所述抗CD3 scFv包含选自以下的CD3结合结构域的可变重链结构域和可变轻链结构域：H1.30_L1.47、H1.32_L1.47、H1.89_L1.47、H1.90_L1.47、H1.33_L1.47、H1.31_L1.47、L1.47_H1.30、L1.47_H1.30、L1.47_H1.32、L1.47_H1.89、L1.47_H1.90、L1.47_H1.33和L1.47_H1.31，并且
其中编号是根据EU编号进行的。
48.根据权利要求47所述的异二聚抗体，其中所述第一变体Fc结构域和所述第二变体Fc结构域各自还包含氨基酸变体428/434S。
49.一种核酸组合物，所述核酸组合物分别包含：
a)第一核酸，所述第一核酸编码根据权利要求31至48中任一项所述的第一单体；
b)第二核酸，所述第二核酸编码根据权利要求31至48中任一项所述的第二单体；和
c)第三核酸，所述第三核酸编码根据权利要求31至48中任一项所述的轻链。
50.一种表达载体组合物，所述表达载体组合物包含：
a)第一表达载体，所述第一表达载体包含根据权利要求49所述的第一核酸；
b)第二表达载体，所述第二表达载体包含根据权利要求49所述的第二核酸；和
c)第三表达载体，所述第三表达载体包含根据权利要求49所述的第三核酸。
51.一种宿主细胞，所述宿主细胞用根据权利要求50所述的表达载体组合物转化。
52.一种制备异二聚抗体的方法，所述方法包括在表达所述抗体的条件下培养根据权利要求51所述的宿主细胞，以及回收所述抗体。
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