WO2018045811A1 - 融合蛋白及其应用 - Google Patents
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- WO2018045811A1 WO2018045811A1 PCT/CN2017/092108 CN2017092108W WO2018045811A1 WO 2018045811 A1 WO2018045811 A1 WO 2018045811A1 CN 2017092108 W CN2017092108 W CN 2017092108W WO 2018045811 A1 WO2018045811 A1 WO 2018045811A1
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Abstract
Description
Claims (28)
- 一种在表面表达嵌合抗原受体的免疫效应细胞,其特征在于,所述免疫细胞还表达式I所示的融合蛋白,Z-A-L-BI其中,Z是任选的信号肽;A是抗体结合区;L是任选的接头部分;B是内吞功能区。
- 一种表达嵌合抗原受体的免疫效应细胞,其特征在于,所述免疫细胞还表达一融合蛋白,该融合蛋白含有抗体结合区和内吞功能区。
- 如权利要求1或2所述的免疫效应细胞,其特征在于,所述的抗体结合区选自以下抗原或其片段:EGFRvIII、EGFR、CD20、CD22、CD19、BCMA、proBDNF前体蛋白、GPC3、CLD18.2、CLD6、间皮素、PD-L1、PD-1、WT-1、IL13Ra2、Her-2、Her-1、Her-3;优选的,所述的抗体结合区含有以下任一氨基酸序列或者含有与以下氨基酸序列具有至少90%、91%、92%、93%、94%、95%、96%、97%、98%、或99%同一性的氨基酸序列:SEQ ID NO:28、29、33、34、35、36、37、38、39、40、41、42、43;更优的,所述的抗体结合区含有以下任一氨基酸序列的活性片段:SEQ ID NO:28、29、33、34、35、36、37、38、39、40、41、42、43。
- 如权利要求3所述的免疫效应细胞,其特征在于,所述抗体结合区与EGFR抗体特异性结合。
- 如权利要求1或2所述的免疫效应细胞,其特征在于,所述内吞功能区衍生自叶酸受体、LDL、CD30、CD33、CD3、EGFR、TFR1;优选衍生自叶酸受体和CD30;更优地,所述内吞功能区具有SEQ ID NO:32或44所示氨基酸序列,或者与SEQ ID NO:32或44具有至少90%、91%、92%、93%、94%、95%、96%、97%、98%、或99%同一性的氨基酸序列,或者为SEQ ID NO:32或44所示的氨基酸序列的活性片段。
- 如权利要求1所述的免疫效应细胞,其特征在于,所述信号肽为叶酸受体信号肽。
- 如权利要求6所述的免疫效应细胞,其特征在于,所述融合蛋白具有SEQ ID NO:10所示的氨基酸序列或者含有与SEQ ID NO:10具有至少90%、91%、92%、93%、94%、95%、96%、97%、98%、或99%同一性的氨基酸序列。
- 如权利要求1或2所述的免疫效应细胞,其特征在于,所述融合蛋白与嵌合抗原受体在免疫效应细胞表面单独表达或融合表达,优选单独表达。
- 一种表达嵌合抗原受体的免疫效应细胞,其特征在于,所述细胞还表达内吞功能区,所述的内吞功能区能将与所述内吞功能区结合的物质转运入所述的免疫效应细胞内。
- 如权利要求9所述的免疫效应细胞,其特征在于,所述内吞功能区衍生自叶酸受体、 LDL、CD30、CD33、CD3、EGFR、TFR1;优选衍生自叶酸受体和CD30;更优地,所述内吞功能区具有SEQ ID NO:32或44所示氨基酸序列,或者与SEQ ID NO:32或44具有至少90%、91%、92%、93%、94%、95%、96%、97%、98%、或99%同一性的氨基酸序列,或者为SEQ ID NO:32或44所示的氨基酸序列的活性片段。
- 如权利要求9或者10所述的免疫效应细胞,其特征在于,所述内吞功能区与嵌合抗原受体在免疫效应细胞表面单独表达或融合表达,优选单独表达。
- 式I所示的融合蛋白,Z-A-L-BI其中,Z是任选的信号肽;A是抗体结合区;L是任选的接头部分;B是内吞功能区。
- 一种融合蛋白,所述融合蛋白包含抗体结合区和内吞功能区。
- 如权利要求12或13所述的融合蛋白,其特征在于,所述的抗体结合区选自以下抗原或其片段:EGFRvIII、EGFR、CD20、CD22、CD19、BCMA、proBDNF前体蛋白、GPC3、CLD18.2、CLD6、间皮素、PD-L1、PD-1、WT-1、IL13Ra2、Her-2、Her-1、Her-3;优选的,所述的抗体结合区含有以下任一氨基酸序列或者含有与以下氨基酸序列具有至少90%、91%、92%、93%、94%、95%、96%、97%、98%、或99%同一性的氨基酸序列:SEQ ID NO:28、29、33、34、35、36、37、38、39、40、41、42、43;更优的,所述的抗体结合区含有以下任一氨基酸序列的活性片段:SEQ ID NO:28、29、33、34、35、36、37、38、39、40、41、42、43。
- 如权利要求14所述的融合蛋白,其特征在于,所述抗体结合区与EGFR抗体特异性结合。
- 如权利要求12或13所述的融合蛋白,其特征在于,所述内吞功能区衍生自叶酸受体、LDL、CD30、CD33、CD3、EGFR、TFR1;优选衍生自叶酸受体和CD30;更优地,所述内吞功能区具有SEQ ID NO:32或44所示氨基酸序列,或者与SEQ ID NO:32或44具有至少90%、91%、92%、93%、94%、95%、96%、97%、98%、或99%同一性的氨基酸序列,或者为SEQ ID NO:32或44所示氨基酸序列的活性片段。
- 如权利要求12所述的融合蛋白,其特征在于,所述信号肽为叶酸受体信号肽。
- 如权利要求17所述的融合蛋白,其特征在于,所述融合蛋白具有SEQ ID NO:10所示的氨基酸序列或者含有与SEQ ID NO:10具有至少90%、91%、92%、93%、94%、95%、96%、97%、98%、或99%同一性的氨基酸序列。
- 如权利要求12-18中任一项所述的融合蛋白的编码核酸。
- 一种表达载体,包含权利要求19所述的编码核酸。
- 一种宿主细胞,包含权利要求20所述的表达载体或基因组中整合有权利要求19所 述的编码核酸。
- 一种免疫辍合物,所述免疫辍合物包括:细胞杀伤性功能部分;和特异性结合权利要求1-8所述免疫效应细胞中的抗体结合区或内吞功能区的抗体或者特异性结合权利要求9-11所述免疫效应细胞中的内吞功能区的抗体。
- 如权利要求22所述免疫辍合物在特异性杀伤权利要求1-11中任一项所述免疫效应细胞中的用途。
- 一种试剂盒,包含权利要求1-11中任一项所述的免疫效应细胞或权利要求22所述的免疫缀合物。
- 特异性清除权利要求1-11中任一项所述免疫效应细胞的方法,所述方法包括给予权利要求22所述的免疫缀合物的步骤。
- 一种分选或富集权利要求1-11中任一项所述的免疫效应细胞的方法,所述方法包括以下步骤:将分选试剂加入包含所述免疫效应细胞的体系,所述分选试剂包含能够特异性结合权利要求1-8所述免疫效应细胞中的抗体结合区或内吞功能区的物质或者特异性结合权利要求9-11所述免疫效应细胞中的内吞功能区的物质;和将结合有所述免疫效应细胞的物质从所述体系分离的步骤。
- 如权利要求26所述的方法,其特征在于,能够特异性结合权利要求1-8所述免疫效应细胞中的抗体结合区或内吞功能区的物质或者特异性结合权利要求9-11所述免疫效应细胞中的内吞功能区的物质固定于固相载体,从而能够实现结合有所述免疫效应细胞的物质从所述体系分离。
- 检测权利要求1-11中任一项所述的免疫效应细胞的方法,所述方法包括:给予特异性结合权利要求1-8所述免疫效应细胞中的抗体结合区或内吞功能区的检测试剂或者特异性结合权利要求9-11所述免疫效应细胞中的内吞功能区的检测试剂,所述检测试剂与可检测标记物相连;和检测所述检测试剂与所述免疫效应细胞形成的复合物。
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CN113238040A (zh) * | 2021-05-18 | 2021-08-10 | 桂林电子科技大学 | 一种基于纳米复合材料的laps传感器检测gpc3方法 |
WO2022028623A1 (zh) | 2020-08-07 | 2022-02-10 | 佧珐药业有限公司 | 工程化改造的细胞以及工程化改造细胞的方法 |
WO2023274303A1 (zh) | 2021-06-29 | 2023-01-05 | 科济生物医药(上海)有限公司 | 调控细胞生理活动的嵌合多肽 |
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CN109180798B (zh) * | 2018-09-04 | 2020-10-27 | 武汉原生药谷生物医药科技有限公司 | 一种增强型治疗性抗体及其应用 |
CN114106183B (zh) * | 2019-01-15 | 2023-06-23 | 浙江道尔生物科技有限公司 | 抗cld18a2纳米抗体及其应用 |
CN110128551A (zh) * | 2019-06-05 | 2019-08-16 | 上海科弈药业科技有限公司 | 一种针对cd19+肿瘤的多功能融合蛋白及其应用 |
CN111944850B (zh) * | 2020-08-28 | 2023-03-31 | 澳门大学 | 表达抗cd22嵌合抗原受体和pd-l1阻断蛋白的细胞的制备方法、表达载体及应用 |
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WO2022028623A1 (zh) | 2020-08-07 | 2022-02-10 | 佧珐药业有限公司 | 工程化改造的细胞以及工程化改造细胞的方法 |
CN113238040A (zh) * | 2021-05-18 | 2021-08-10 | 桂林电子科技大学 | 一种基于纳米复合材料的laps传感器检测gpc3方法 |
CN113238040B (zh) * | 2021-05-18 | 2022-05-31 | 桂林电子科技大学 | 一种非诊断目的基于纳米复合材料的laps传感器检测gpc3方法 |
WO2023274303A1 (zh) | 2021-06-29 | 2023-01-05 | 科济生物医药(上海)有限公司 | 调控细胞生理活动的嵌合多肽 |
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