CN105816855A - 用于诱发单核细胞免疫应答的重组lag-3或其衍生物的应用 - Google Patents

用于诱发单核细胞免疫应答的重组lag-3或其衍生物的应用 Download PDF

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CN105816855A
CN105816855A CN201610221687.0A CN201610221687A CN105816855A CN 105816855 A CN105816855 A CN 105816855A CN 201610221687 A CN201610221687 A CN 201610221687A CN 105816855 A CN105816855 A CN 105816855A
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弗雷德里克·特里贝尔
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Abstract

本申请涉及用于诱发单核细胞免疫应答的重组LAG?3或其衍生物的应用。本发明涉及重组LAG?3或其衍生物的应用,以促进单核细胞介导的免疫应答,特别是诱发血液中单核细胞数量的增加。该发现用于治疗感染性疾病或癌症的新型治疗试剂的开发。

Description

用于诱发单核细胞免疫应答的重组LAG-3或其衍生物的应用
本申请是申请日为2008年10月3日、申请号为“200880117476.6”、发明名称为“用于诱发单核细胞免疫应答的重组LAG-3或其衍生物的应用”的中国专利申请的分案申请,原申请是国际申请PCT/IB2008/002653的中国国家阶段申请。
技术领域
本发明涉及重组LAG-3或其衍生物的应用以促进单核细胞介导的免疫应答。
本发明使血液中单核细胞的数量增加。
本发明发现了多种应用,特别是在癌症免疫治疗中的新型治疗试剂的开发应用。
参考文献参见随附在说明书后面方括号[]中的参考文献。
背景技术
在人CD4+和CD8+活化的T细胞中以及在活化的NK细胞中表达的淋巴细胞活化基因3(hlag-3)编码503个氨基酸1型膜蛋白(LAG-3)以及四个细胞外免疫球蛋白超家族(IgSF)结构域[1]。克隆了小鼠淋巴细胞活化基因3(mlag-3)并且发现与hlag-3有大约70%的同源性,在细胞质内的氨基酸链中具有相同的富含脯氨酸结构。
正如MHC II类的天然高度亲和配体描述的,LAG-3(CD223)已知在体外诱导单核细胞衍生的树突状细胞的成熟,并且在体内用作免疫治疗佐剂诱导CD41型辅助性T细胞反应和CD8T细胞反应[2]。关于LAG-3和其用作免疫刺激剂的进一步信息可在TRIEBELE等人[1]、TRIEBEL等人[3]以及HUARD等人[4]的著作中找到。
可溶性LAG-3的一些形式能够与MHC II类分子结合并且能够诱导树突状细胞成熟并迁移至次级淋巴器官,在次级淋巴器官中它们能够启动导致肿瘤排斥的原态CD4-辅助和CD8细胞毒性T细胞[5]。
最近,重组可溶性人LAG-3Ig融合蛋白显示在先天性免疫应答和获得性免疫应答中均能激活大范围的效应器细胞,例如诱导单核细胞-巨噬细胞分泌细胞因子/趋化因子[6]。
单核细胞由来自称为成单核细胞的造血干细胞前体的骨髓生成。它们在血液中构成了3%-8%之间的白细胞。单核细胞在血流中循环约24小时(8小时的半衰期),随后通常进入全身组织中。在组织中,单核细胞成熟为巨噬细胞、上皮状细胞或抗原提呈细胞(APCs,例如树突状细胞)。单核细胞负责体内外来物质的吞噬(吸收)。单核细胞能够使用中间(调理作用)蛋白例如包被病原体的抗体或补体,以及通过经识别病原体的模式识别受体直接与病原体结合,从而进行吞噬作用。单核细胞还能够通过抗体杀死感染的宿主细胞,称为抗体依赖性细胞介导的细胞毒性(ADCC)。由于它们的分泌作用和吞噬作用特性,单核细胞-巨噬细胞存在于非特异性和特异性免疫应答中。
膜标记物的研究允许识别单核细胞群体,无论是成熟的或未成熟的、营养缺陷的或非营养缺陷的。存在于单核细胞膜(成熟的或未成熟的)上的分子几乎总是非特异性的而是与以下活性相对应:
-IgG的Fc片段的受体(CD16、CD32、CD64),
-IgE的Fc片段的受体(CD23),
-补体片段的受体(CD11b,CD21/CD35),
-白细胞粘附蛋白(CD11a,CD11c),
-促进与革兰氏细菌的LPS结合的蛋白(CD14),
-具有酪氨酸磷酸酶活性的蛋白(CD45)。
发明内容
目前,本发明的发明人完全意外地发现了当接种至高度恶性的肿瘤患者时人LAG-3或其衍生物,例如转移性乳腺癌(MBC)或转移性肾透明细胞癌(MRCC)患者体内时诱导单核细胞依赖性的强效免疫力。
所述诱导的免疫力通过血液中单核细胞计数的显著增加表现自身。
该结果通过多次将LAG-3或其衍生物施入接受免疫治疗或化学免疫治疗的患者体内的方式来获得。
该结果相当令人吃惊,因为在与单核细胞结合和单核细胞活化之后的单核细胞扩增是非预期的。事实上,单核细胞是结束分化的造血细胞并且不能增殖。它们能够作为单核细胞或在不同细胞因子的影响下朝着巨噬细胞或树突状细胞分化而停留在血液里,直至它们死亡。因此,可以相信在不受以下理论的限制下涉及的作用机理可以是针对存在于骨髓中的造血前体细胞(在前单核细胞阶段之前)的增殖信号,或者是成熟循环单核细胞的半衰期或停留时间的增加。
因此,本发明涉及在制备用于治疗感染性疾病或癌症的诱导单核细胞数量增加的药物中诱发单核细胞介导的免疫应答的重组LAG-3或其衍生物的应用。
从本发明意义上而言,“LAG-3的衍生物”是指LAG-3的突变体、变型或片段,假设它们保持与MHC II类分子结合的LAG-3的能力。
因此,可使用LAG-3的以下形式:
-全部LAG-3蛋白;
-由四个免疫球蛋白细胞外结构域中的至少一个所组成的其可溶性多肽片段,即在法国专利申请FR9000126中公开的、由从LAG-3序列的第23位氨基酸延伸至第448位氨基酸的细胞外区域组成的LAG-3的可溶性部分;
-基本上由所有的第一个和第二个结构域组成的LAG-3的片段;
-基本上由所有的第一个和第二个结构域或者所有四个结构域组成的LAG-3的片段,例如在WO95/30750中定义的;
-可溶性LAG-3的突变形式或者包含D1和D2细胞外结构域并且由以下位点的氨基酸置换组成的其片段:
*在以下位点之一的氨基酸置换:
73位,ARG被GLU置换;
75位,ARG被ALA或GLU置换;
76位,ARG被GLU置换;
或者两个或多个这些置换的组合;
*在以下位点之一的氨基酸置换:
30位,ASP被ALA置换;
56位,HIS被ALA置换;
77位,TYR被PHE置换;
88位,ARG被ALA置换;
103位,ARG被ALA置换;
109位,ASP被GLU置换;
115位,ARG被ALA置换;
或者54位和66位之间包含的区域的缺失;
或者两个或多个这些置换的组合。
HUARD等人(Proc.Natl.Acad.Sci.USA,11:5744-5749,1997)描述了这些突变体。
-由含D1、D2和D3的可溶性52kDa蛋白组成的LAG-3的生理变型。
-重组可溶性人LAG-3Ig融合蛋白(IMP321),一种在采用质粒转染的中国仓鼠卵巢细胞中生产的200kDa二聚体,该质粒编码与人IgGlFc融合的hLAG-3的细胞外结构域。
从本发明意义上而言,“药物”是指有效多剂量的重组LAG-3蛋白或其衍生物。
从本发明意义上而言,“有效多剂量的重组LAG-3蛋白或其衍生物”是指允许每一至几周施用一剂重组LAG-3蛋白或其衍生物,持续至少12周,优选地持续至少24周,由13天±2天停药间隔期所隔开的制剂。优选地,施药为每两周方案。
从本发明意义上而言,“一剂重组LAG-3蛋白或其衍生物”是指允许一次施药在0.25~30mg范围内,优选地1~6.25mg,更优选地6~30mg,例如,向体重指数(体重/身高2)在18~30kg/m2范围内的患者根据需要施用大约1.25mg的重组LAG-3蛋白或其衍生物。
通过将它们进行全身性接种例如作为皮下、肌肉或静脉注射,优选地作为皮下注射,以游离形式例如以溶液形式施用重组LAG-3蛋白或其衍生物。
所述重组LAG-3蛋白或其衍生物还可以进行配制,以便允许与具有抗癌或抗感染疾病免疫治疗或化学治疗特性的化合物一起施用。
从本发明意义上而言,“与化合物一起施用”是指在施用所述化合物之前、过程中或者之后施用重组LAG-3蛋白或其衍生物。
从本发明意义上而言,“具有抗癌或抗感染疾病化学治疗特性的化合物”是指,例如选自紫杉醇类(紫杉醇和多西紫杉醇)、吉西他滨和蒽环类(阿霉素)的化疗试剂或者抗病毒试剂例如利巴韦林。
在本发明的具体实施例中,在第一次施用具有抗癌或抗感染疾病化学治疗特性的细胞毒性化合物之后,给患者施用重组LAG-3蛋白或其衍生物。
优选地,在施用具有抗癌或抗感染疾病化学治疗特性的细胞毒性化合物之后12~96小时,给患者施用重组LAG-3蛋白或其衍生物。
在另一实施例中,在第一次施用具有抗癌或抗感染疾病化学治疗特性的细胞毒性化合物之后一或两天,给患者施用重组LAG-3蛋白或其衍生物。
在本发明的另一具体实施例中,同时、单独或序贯地施用重组LAG-3蛋白或其衍生物和具有抗癌或抗感染疾病化学治疗特性的细胞毒性化合物。
优选地,在本发明的该具体实施例中,施用重组LAG-3蛋白或其衍生物至少6次,例如7次、10次,12次或更多。
优选地,在本发明的该具体实施例中,按照每两周方案施用重组LAG-3蛋白或其衍生物。
优选地,以包含0.25~30mg之间的剂量,最终以包含6~30mg之间的剂量、最终以包含8~25mg之间的剂量、最终以包含介于12~20mg之间的剂量施用重组LAG-3蛋白或其衍生物。
从本发明意义上而言,“具有抗癌或抗感染疾病化学治疗特性的化合物”也指,例如选自由通过ADCC(抗体依赖性细胞毒性)杀死肿瘤细胞的治疗抗体的化合物组成的组,以及其混合物,优选地选自由利妥昔单抗、西妥昔单抗、依决洛单抗和曲妥珠单抗组成的组。
在本发明的具有实施例中,将重组LAG-3蛋白或其衍生物同时、单独或序贯地施予患者。
优选地,在本发明的具有实施例中,重组LAG-3蛋白或其衍生物与治疗抗体在同一天施用。
本发明还涉及试剂盒,即包含用于同时、单独或序贯使用的重组LAG-3蛋白或其衍生物与治疗抗体的组合制剂。
优选地,该试剂盒包含重组LAG-3蛋白或其衍生物和选自由利妥昔单抗、西妥昔单抗、依决洛单抗和曲妥珠单抗组成的组的治疗抗体。
优选地,本发明的试剂盒包含重组LAG-3蛋白或其衍生物和利妥昔单抗。
本发明的试剂盒中,由于两种组分之间的协同细胞毒性作用,重组LAG-3蛋白或其衍生物和治疗抗体形成功能统一体。这种效应是一种新的联合效应,因为在单独施用两种组分时不产生与作为组合制剂施用时相同的效应。
本发明还涉及试剂盒,即包含重组LAG-3蛋白或其衍生物和具有抗癌或抗感染疾病化学治疗特性的组合制剂,用于同时、单独或序贯使用。
优选地,本发明的试剂盒包含重组LAG-3蛋白或其衍生物和选自由紫杉醇类(紫杉醇和多西紫杉醇)、吉西他滨和蒽环类(阿霉素)组成的组的具有抗癌或抗感染疾病化学治疗特性的化合物。
本发明还涉及用于治疗涉及单核细胞介导的免疫应答的病理状态的方法,包括根据患者的需要,向其施用如上定义的药物。
从本发明意义上而言,“涉及单核细胞介导的免疫应答的病理状态”是指病毒感染性疾病、寄生感染性疾病、细菌感染性疾病、以及癌症。
通过以下给出的非限制性实例,本发明的其他优点对于本领域的技术人员来说也可以是显而易见的,并通过附图示出。
附图说明
图1表示来自转移性乳腺癌患者的PBMC中单核细胞(即CD14+CD45+细胞)的荧光激活细胞分选(FACS)分析。
图2表示来自转移性乳腺癌患者的新鲜全血中单核细胞(即CD14+CD45+细胞)的荧光激活细胞分选(FACS)分析。
图3表示来自转移性肾细胞癌患者的新鲜全血中单核细胞(即CD14+CD45+细胞)的荧光激活细胞分选(FACS)分析。
图4表示来自转移性乳腺癌患者的新鲜全血中单核细胞(即CD14+CD45+细胞)的荧光激活细胞分选(FACS)分析。
图5表示在转移性肾细胞癌患者血浆中通过ELISA法测定的IMP321的药代动力学曲线。
图6表示用利妥昔单抗和/或IMP321在不同条件下培养的PBMC的流式细胞仪分析。
具体实施方式
实施例1:使用低IMP321剂量在转移性乳腺癌(MBC)患者中单核细胞的增加
接受已知诱导肿瘤细胞吞噬作用的5例MBC患者,在每两周一次的化学治疗之后1-2天分别接受一剂皮下注射IMP321,剂量为0.25mg,持续24周,通过14天的停药间隔期隔开。
在最后一次注射IMP321(即,观察产品的持续性免疫调节效应)后14天、在3个月(第85天)和6个月(第170天)采集每例患者的血液样品置于肝素锂采血管(Vacutainer;BDBiosciences)中。使用LeucoSep管(Greiner Bio-One)在Ficoll-Paque梯度(Pharmacia)上分离PBMC,并立即使用。
在所述新鲜PBMC样品(因为单核细胞对冷冻敏感)中,通过荧光激活细胞分选(FACS)法分析单核细胞数量的增加,并与在IMP321施用(第1天)之前采集的基于新鲜PBMC样品进行的单核细胞计数进行比较。
结果见图1。
结果表明,在这种低IMP321剂量临床方案下,单核细胞计数平均增加2.5倍(在3个月,第85天)和3.5倍(在6个月,第170天)。
为了证实上述结果,采用了更加直接和很可能更加准确的方法,该方法通过首先测定采用稀释的荧光微珠进行分析的血液的准确体积并且随后计数存在于该全血量中的门控CD45+(白细胞)中的CD14+细胞(即单核细胞)的数量在体外直接定量全血细胞中单核细胞的数量(即未事先在Ficoll梯度上纯化的PBMC)。
结果见图2。
结果表明,当以低剂量(0.25mg)给予IMP321持续很长的时间,即6个月,注射12次时,单核细胞计数在第170天平均增加44倍(在第85天为2.8倍),表明靶向的MHC II+类单核细胞样造血细胞的强而直接的刺激作用。
实施例2:使用高IMP321剂量在转移性肾透明细胞癌(MRCC)患者中单核细胞的增加3例MRCC患者分别接受一次皮下注射IMP321,剂量为6.25mg,每两周一次,持续12周,通过14天的停药间隔期隔开。
采用如上所述的方法,在最后一次注射IMP321之后14天(即,观察产品的持续性免疫调节效应)、在2个月(第57天)和3个月(第85天),采集每例患者的血液样品,并立即使用。
在新鲜血液样品中(因为单核细胞对冷冻敏感),通过FACS分析CD14+CD45+细胞的扩增,并与基于在施用IMP321(第1天)之前采集的新鲜血液样品进行的单核细胞计数进行比较。
结果见图3。
结果表明,采用该种高IMP321剂量临床方案,单核细胞计数平均增加2倍(在3个月,第85天),在该临床方案中,患者仅接受6次注射。
实施例3:在接受紫杉醇和IMP321剂量的转移性乳腺癌患者中单核细胞的增加
在28天疗程的第1、8和15天接受作为转移性乳腺癌6个疗程紫杉醇(静脉注射给予80mg/m2)的一线化疗的患者,在每个28疗程的第2和16天接受皮下注射IMP3211-30mg。或者在第3或17天施用IMP321。
因此,每例患者接受了每周1次紫杉醇和12次皮下注射IMP321的标准6个月疗程,在每两周方案中施用紫杉醇后1至2天给予每次注射。
与第1天比较,在最后一次注射后14天,在3个月(第85天)和6个月(第170天)通过荧光激活细胞分选(FACS)法分析每微升新鲜血液中绝对单核细胞计数的增加。
在注射低剂量IMP321(1.25mg)的患者中获得的结果见图4。
这些数据表明,在大多数患者(如果不是全部)中1.25mg的剂量(图4)诱导血液中单核细胞亚群库的扩增。
预计IMP321的最佳剂量方案将是介于6和30mg/注射之间。
基于在转移性肾细胞癌患者中获得的药代动力学数据结果(图5),这些剂量已经表明是安全的并且给出可接受的全身暴露量。在接受大于6mg的IMP321剂量注射的患者中,在皮下注射后至少24小时可获得高于1ng/ml的IMP321的血液浓度(图5)。
实施例4:接受吉西他滨和IMP321剂量的晚期胰腺癌患者的治疗
在28天疗程的第1、8和15天接受作为晚期胰腺癌6个疗程标准吉西他滨(30分钟内静脉注射1mg/m2)的一线化疗的患者(或者不符合外科手术移除肿瘤的患者),在每个28疗程的第2和16天另外接受6至30mg皮下注射IMP321。或者,在第3或17天施用IMP321。
因此,每例患者接受了吉西他滨和12次皮下注射IMP321的标准6个月疗程,在每两周方案中吉西他滨施用后1至2天给予每次注射。
如实施例1所述的方法,通过荧光激活细胞分选(FACS)法分析单核细胞的数量。
实施例5:通过低剂量IMP321诱导利妥昔单抗介导的ADCC的增加
首先,将PBMC与IL-2(100U/ml),含或不含IMP321(浓度为0μg/ml、0.03μg/ml或0.1μg/ml)一起孵育40个小时。然后,在靶细胞(即人CD20+Raji B细胞)存在下,将PBMC与增加浓度的利妥昔单抗(0、0.5和5μg/ml)一起孵育。
首先采用CFSE(羧基荧光素琥珀酰亚胺酯)标记Raji细胞,在添加0、0.5和5μg/ml的利妥昔单抗的培养基中孵育并与效应器细胞以效应器-靶细胞25∶1的比率,在37℃下共培养6小时。
然后,将细胞与7-AAD(7-氨基-放线菌素-D)一起在冰上孵育15min并通过流式细胞仪进行分析以确定死亡的CFSE+7-AAD+Raji靶细胞的百分比(即细胞毒性%)。
结果见图6。
增加利妥昔单抗的浓度增加了细胞毒性的百分比,清楚地表明剂量依赖性ADCC活性。
当添加0.03或0.1μg/ml IMP321时,细胞毒性的比例大大提高。例如,在0.1μg/mlIMP321存在下,采用0.5μg/ml利妥昔单抗观察到30%的细胞毒性,该30%细胞毒性高于在缺乏IMP321时采用5μg/ml利妥昔单抗获得的25%细胞毒性值。
因此,添加0.1μg/ml IMP321可能具有10-15倍的利妥昔单抗活性,因为当添加低剂量IMP321(0.1μg/ml)时采用小于10倍的抗体获得优良的细胞毒性。
这些数据显示利妥昔单抗和IMP321之间的协同作用。
以下内容对应于原申请的权利要求书:
1.一种在制备用于治疗感染性疾病或癌症的诱导单核细胞数量增加的药物中诱发单核细胞介导的免疫应答的重组LAG-3或其衍生物的用途。
2.根据权利要求1的用途,其中,所述药物由有效剂量的重组LAG-3蛋白或其衍生物组成。
3.根据权利要求2的用途,其中,配制所述剂量的重组LAG-3蛋白或其衍生物以便允许每1至几周施用一剂量,持续至少12周,优选地持续至少24周,通过13天±2天停药间隔期隔开。
4.根据权利要求2或3的用途,其中,配制所述剂量的重组LAG-3蛋白或其衍生物以便允许向体重指数(体重/身高2)在18~30kg/m2范围内的患者根据其需要皮下或静脉施用范围为0.25~30mg,优选地为6~30mg的重组LAG-3蛋白或其衍生物。
5.根据权利要求2~4中任一项的用途,其中,配制所述剂量的重组LAG-3蛋白或其衍生物以便允许与具有抗癌或者抗感染疾病免疫治疗或者化学治疗特性的化合物一起施用。
6.根据权利要求5的用途,其中,重组LAG-3蛋白或其衍生物的剂量包含0.25~30mg,优选地6~30mg的所述重组LAG-3蛋白或其衍生物。
7.根据权利要求5或6的用途,其中,所述化合物选自化疗试剂。
8.根据权利要求7的用途,其中,所述化疗试剂选自由例如紫杉醇和多西紫杉醇的紫杉醇类,例如阿霉素的蒽环类,以及吉西他滨组成的组。
9.根据权利要求5或6的用途,其中,所述化合物选自由通过ADCC(抗体-依赖性细胞-介导的细胞毒性)杀死肿瘤细胞的治疗抗体、以及其混合物组成的组。
10.根据权利要求9的用途,其中,所述治疗抗体选自由利妥昔单抗、西妥昔单抗、依决洛单抗和曲妥珠单抗组成的组。
11.试剂盒,包含重组LAG-3蛋白或其衍生物和如权利要求9或10中所述的治疗抗体,用于同时、单独或序贯使用。
12.试剂盒,包含重组LAG-3蛋白或其衍生物和如权利要求7或8中所述的具有抗癌化学治疗特性的化合物,用于同时、单独或序贯使用。
参考文献
[1]TRIEBEL et al.,J.Exp.Med.,171:1393-1405,1990
[2]BRIGNONE et al.,J.Immune Based Ther Immunotherapies,5:5,2007
[3]TRIEBEL et al.,Trends Immunol.,24:619-622,2003
[4]HUARD et al.,Proc.Natl.Acad.Sci.USA,94:5744-5749,1997
[5]PRIGENT et al.,Eur.J.Immunol.,29:3867-3876,1999
[6]BRIGNONE et al.,J.Immunol.,179:4202-4211,2007

Claims (23)

1.制剂,其包含有效多剂量的诱发单核细胞介导之免疫应答的重组LAG-3蛋白或其衍生物。
2.根据权利要求1所述的制剂,其中每个剂量的重组LAG-3蛋白或衍生物包含0.25-30mg摩尔当量的重组可溶性人LAG-3Ig融合蛋白IMP321。
3.根据权利要求1所述的制剂,其中每个剂量的重组LAG-3蛋白或衍生物包含6-30mg摩尔当量的重组可溶性人LAG-3Ig融合蛋白IMP321。
4.根据任一前述权利要求所述的制剂,其中配制所述有效多剂量的重组LAG-3蛋白或其衍生物以便允许每1至几周施用一剂量,持续至少12周,优选地持续至少24周,通过13天±2天停药间隔期隔开。
5.根据任一前述权利要求所述的制剂,其中配制每一剂量重组LAG-3蛋白或其衍生物以便允许皮下或静脉施用。
6.根据任一前述权利要求所述的制剂,其中所述重组LAG-3蛋白或其衍生物是指重组可溶性人LAG-3Ig融合蛋白。
7.诱发单核细胞介导之免疫应答的重组LAG-3蛋白或其衍生物与具有抗癌或抗感染疾病免疫治疗或化学治疗特性的化合物的组合制剂在制备用于感染性疾病或者癌症治疗的诱导单核细胞数量增加的药物中的用途,其中配制由有效多剂量的重组LAG-3蛋白或其衍生物组成的药物,以便允许在施用具有抗癌或者抗感染性疾病的免疫治疗或者化学治疗特性的化合物之前/过程中/之后施用。
8.根据权利要求7所述的用途,其中每个剂量的重组LAG-3蛋白或衍生物包含0.25-30mg摩尔当量的重组可溶性人LAG-3Ig融合蛋白IMP321。
9.根据权利要求7所述的用途,其中每个剂量的重组LAG-3蛋白或衍生物包含6-30mg摩尔当量的重组可溶性人LAG-3Ig融合蛋白IMP321。
10.根据权利要求7至9中任一项所述的用途,其中所述化合物选自化疗试剂。
11.根据权利要求10所述的用途,其中所述化疗试剂选自紫杉醇类、蒽环类、以及吉西他滨。
12.根据权利要求11所述的用途,其中所述紫杉醇类为紫杉醇或多西紫杉醇。
13.根据权利要求11所述的用途,其中所述蒽环类为阿霉素。
14.根据权利要求7至9中任一项所述的用途,其中所述化合物选自通过ADCC(抗体-依赖性细胞-介导的细胞毒性)杀死肿瘤细胞的治疗抗体、以及其混合物。
15.根据权利要求14所述的用途,其中所述治疗抗体选自利妥昔单抗、西妥昔单抗、依决洛单抗和曲妥珠单抗。
16.根据权利要求7至15中任一项所述的用途,其中所述重组LAG-3蛋白或其衍生物是指重组可溶性人LAG-3Ig融合蛋白。
17.试剂盒,其包含重组LAG-3蛋白或其衍生物和化疗试剂,用于同时、单独或序贯使用。
18.根据权利要求17所述的试剂盒,其中所述化疗试剂选自紫杉醇类、蒽环类、以及吉西他滨。
19.根据权利要求18所述的试剂盒,其中所述紫杉醇类为紫杉醇或多西紫杉醇。
20.根据权利要求18所述的试剂盒,其中所述蒽环类为阿霉素。
21.试剂盒,其包含重组LAG-3蛋白或其衍生物和治疗抗体,用于同时、单独或序贯使用,其中所述治疗抗体选自通过ADCC(抗体-依赖性细胞-介导的细胞毒性)杀死肿瘤细胞的治疗抗体、以及其混合物。
22.根据权利要求21所述的试剂盒,其中所述治疗抗体选自利妥昔单抗、西妥昔单抗、依决洛单抗和曲妥珠单抗。
23.根据权利要求17至22中任一项所述的试剂盒,其中所述重组LAG-3蛋白或其衍生物是指重组可溶性人LAG-3Ig融合蛋白。
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110950966A (zh) * 2019-12-13 2020-04-03 启辰生生物科技(珠海)有限公司 融合蛋白、编码核酸和细胞及用途
US10954246B2 (en) 2017-04-13 2021-03-23 Taizhou Eoc Pharma Co., Ltd. Compound of EOC315 Mod.I crystal form and preparation method thereof

Families Citing this family (292)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2044949A1 (en) * 2007-10-05 2009-04-08 Immutep Use of recombinant lag-3 or the derivatives thereof for eliciting monocyte immune response
ES2671748T3 (es) 2011-07-21 2018-06-08 Tolero Pharmaceuticals, Inc. Inhibidores heterocíclicos de proteína quinasas
SG11201508358RA (en) 2013-04-09 2015-11-27 Boston Biomedical Inc 2-acetylnaphtho[2,3-b]furan -4,9-dione for use on treating cancer
JP2016531907A (ja) 2013-08-02 2016-10-13 アデュロ・バイオテック・ホールディングス・ヨーロッパ・ベスローテン・フエンノートシャップAduro Biotech Holdings, Europe B.V. 免疫刺激のためのcd27アゴニストと免疫チェックポイント阻害との組み合わせ
GB201322626D0 (en) * 2013-12-19 2014-02-05 Immutep S A Combined preparations for the treatment of cancer
DK3466949T3 (da) 2013-12-24 2021-03-15 Bristol Myers Squibb Co Tricyklisk forbindelse som anticancermidler
JOP20200094A1 (ar) 2014-01-24 2017-06-16 Dana Farber Cancer Inst Inc جزيئات جسم مضاد لـ pd-1 واستخداماتها
EP3116909B1 (en) 2014-03-14 2019-11-13 Novartis Ag Antibody molecules to lag-3 and uses thereof
SG10201810507WA (en) 2014-06-06 2018-12-28 Bristol Myers Squibb Co Antibodies against glucocorticoid-induced tumor necrosis factor receptor (gitr) and uses thereof
BR112016028255A2 (pt) 2014-06-06 2017-08-22 Flexus Biosciences Inc agentes imunorreguladores
JO3663B1 (ar) 2014-08-19 2020-08-27 Merck Sharp & Dohme الأجسام المضادة لمضاد lag3 وأجزاء ربط الأنتيجين
UY36390A (es) 2014-11-05 2016-06-01 Flexus Biosciences Inc Compuestos moduladores de la enzima indolamina 2,3-dioxigenasa (ido), sus métodos de síntesis y composiciones farmacéuticas que los contienen
JP2017538678A (ja) 2014-11-05 2017-12-28 フレクサス・バイオサイエンシーズ・インコーポレイテッドFlexus Biosciences, Inc. 免疫調節剤
UY36391A (es) 2014-11-05 2016-06-01 Flexus Biosciences Inc Compuestos moduladores de la enzima indolamina 2,3-dioxigenasa (ido1), sus métodos de síntesis y composiciones farmacèuticas que las contienen
AR103232A1 (es) 2014-12-22 2017-04-26 Bristol Myers Squibb Co ANTAGONISTAS DE TGFbR
GB201500374D0 (en) 2015-01-09 2015-02-25 Immutep S A Combined preparations for the treatment of cancer
MA41463A (fr) * 2015-02-03 2017-12-12 Anaptysbio Inc Anticorps dirigés contre le gène d'activation 3 des lymphocytes (lag-3)
US10983128B2 (en) 2015-02-05 2021-04-20 Bristol-Myers Squibb Company CXCL11 and SMICA as predictive biomarkers for efficacy of anti-CTLA4 immunotherapy
KR20170122799A (ko) 2015-03-02 2017-11-06 리겔 파마슈티칼스, 인크. TGF-β 억제제
WO2016146143A1 (en) 2015-03-16 2016-09-22 Amal Therapeutics Sa Cell penetrating peptides and complexes comprising the same
PE20180117A1 (es) 2015-04-03 2018-01-18 Bristol Myers Squibb Co Inhibidores de indolamina-2,3-dioxigenasa para el tratamiento de cancer
WO2016162505A1 (en) 2015-04-08 2016-10-13 F-Star Biotechnology Limited Her2 binding agent therapies
CN114681608A (zh) 2015-04-13 2022-07-01 戊瑞治疗有限公司 癌症组合疗法
ES2905525T3 (es) 2015-05-06 2022-04-11 Snipr Tech Ltd Alteración de poblaciones microbianas y modificación de la microbiota
US10683290B2 (en) 2015-05-11 2020-06-16 Bristol-Myers Squibb Company Tricyclic compounds as anticancer agents
US9725449B2 (en) 2015-05-12 2017-08-08 Bristol-Myers Squibb Company Tricyclic compounds as anticancer agents
EP3307740B1 (en) 2015-05-12 2019-12-18 Bristol-Myers Squibb Company 5h-pyrido[3,2-b]indole compounds as anticancer agents
PE20180926A1 (es) 2015-05-29 2018-06-08 Bristol Myers Squibb Co Anticuerpos contra el miembro 4 de la superfamilia del receptor del factor de necrosis tumoral (ox40) y sus usos
MX2017015618A (es) 2015-06-03 2018-08-15 Boston Biomedical Inc Composiciones que comprenden un inhibidor de la autorrenovación y diferenciación de células madre cancerosas y un agente inmunoterapéutico para su uso en el tratamiento del cáncer.
KR20180034548A (ko) 2015-07-28 2018-04-04 브리스톨-마이어스 스큅 컴퍼니 Tgf 베타 수용체 길항제
CN108349976A (zh) 2015-08-25 2018-07-31 百时美施贵宝公司 TGFβ受体拮抗剂
EP3798234A1 (en) 2015-09-02 2021-03-31 Immutep S.A.S. Anti-lag-3 agonistic antibodies
US10265379B2 (en) * 2015-09-16 2019-04-23 Annabelle Rodriguez Oquendo Use of recombinant lymphocyte activation gene-3 as a companion therapeutic for patients at risk for cardiovascular disease and other chronic inflammatory diseases
US10149887B2 (en) 2015-10-23 2018-12-11 Canbas Co., Ltd. Peptides and peptidomimetics in combination with t cell activating and/or checkpoint inhibiting agents for cancer treatment
JP6936221B2 (ja) 2015-11-02 2021-09-15 ファイブ プライム セラピューティクス, インコーポレイテッド Cd80細胞外ドメインポリペプチドと、がん治療でのそれらの使用
CA3004530A1 (en) 2015-11-07 2017-05-11 Multivir Inc. Methods and compositions comprising tumor suppressor gene therapy and immune checkpoint blockade for the treatment of cancer
WO2017087678A2 (en) 2015-11-19 2017-05-26 Bristol-Myers Squibb Company Antibodies against glucocorticoid-induced tumor necrosis factor receptor (gitr) and uses thereof
RU2021107536A (ru) 2015-11-23 2021-07-02 Файв Прайм Терапьютикс, Инк. Ингибиторы fgfr2 отдельно или в комбинации с иммуностимулирующими агентами в лечении рака
JP6856648B2 (ja) 2015-12-15 2021-04-07 ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company Cxcr4受容体アンタゴニスト
RU2018123481A (ru) 2015-12-16 2020-01-20 Мерк Шарп И Доум Корп. Анти-lag3 антитела и антигенсвязывающие фрагменты
US20190175748A1 (en) 2016-03-16 2019-06-13 Amal Therapeutics Sa Combination of an immune checkpoint modulator and a complex comprising a cell penetrating peptide, a cargo and a tlr peptide agonist for use in medicine
EA201892362A1 (ru) 2016-04-18 2019-04-30 Селлдекс Терапьютикс, Инк. Агонистические антитела, которые связываются с cd40 человека, и варианты их применения
WO2017192815A1 (en) 2016-05-04 2017-11-09 Bristol-Myers Squibb Company Inhibitors of indoleamine 2,3-dioxygenase and methods of their use
CN109348714A (zh) 2016-05-04 2019-02-15 百时美施贵宝公司 吲哚胺2,3-双加氧酶的抑制剂及其使用方法
WO2017192813A1 (en) 2016-05-04 2017-11-09 Bristol-Myers Squibb Company Inhibitors of indoleamine 2,3-dioxygenase and methods of their use
CN109414421A (zh) 2016-05-04 2019-03-01 百时美施贵宝公司 吲哚胺2,3-双加氧酶的抑制剂及其使用方法
EP3452029A4 (en) 2016-05-04 2019-10-30 Bristol-Myers Squibb Company INDOLEAMINE 2,3-DIOXYGENASE INHIBITORS AND METHODS OF USE
GB201609811D0 (en) 2016-06-05 2016-07-20 Snipr Technologies Ltd Methods, cells, systems, arrays, RNA and kits
SG11201900026TA (en) 2016-07-14 2019-01-30 Bristol Myers Squibb Co Antibodies against tim3 and uses thereof
WO2018017633A1 (en) 2016-07-21 2018-01-25 Bristol-Myers Squibb Company TGF Beta RECEPTOR ANTAGONISTS
US11351164B2 (en) 2016-08-26 2022-06-07 Bristol-Myers Squibb Company Inhibitors of indoleamine 2,3-dioxygenase and methods of their use
US20190255165A1 (en) 2016-09-21 2019-08-22 Amal Therapeutics Sa Fusion Comprising A Cell Penetrating Peptide, A Multi Epitope And A TLR Peptide Agonist For Treatment Of Cancer
AU2017335732A1 (en) 2016-09-27 2019-04-04 Board Of Regents, The University Of Texas System Methods for enhancing immune checkpoint blockade therapy by modulating the microbiome
JP7041136B2 (ja) 2016-10-12 2022-03-23 ボード オブ リージェンツ,ザ ユニバーシティ オブ テキサス システム Tusc2免疫療法のための方法および組成物
US10660909B2 (en) 2016-11-17 2020-05-26 Syntrix Biosystems Inc. Method for treating cancer using chemokine antagonists
WO2018094275A1 (en) 2016-11-18 2018-05-24 Tolero Pharmaceuticals, Inc. Alvocidib prodrugs and their use as protein kinase inhibitors
CA3045306A1 (en) 2016-11-29 2018-06-07 Boston Biomedical, Inc. Naphthofuran derivatives, preparation, and methods of use thereof
WO2018099539A1 (en) 2016-11-29 2018-06-07 Horst Lindhofer Combination of t-cell redirecting multifunctional antibodies with immune checkpoint modulators and uses thereof
CN110381997A (zh) 2016-12-12 2019-10-25 茂体外尔公司 用于治疗和预防癌症和感染性疾病的包含病毒基因治疗和免疫检查点抑制剂的方法和组合物
CN108204958A (zh) * 2016-12-19 2018-06-26 伊缪泰普有限公司 结合测定
US10961239B2 (en) 2017-01-05 2021-03-30 Bristol-Myers Squibb Company TGF beta receptor antagonists
EP3570844B1 (en) 2017-01-20 2023-09-06 Arcus Biosciences, Inc. Azolopyrimidine for the treatment of cancer-related disorders
CA3057687A1 (en) 2017-03-31 2018-10-04 Five Prime Therapeutics, Inc. Combination therapy for cancer using anti-gitr antibodies
KR20190137911A (ko) 2017-04-21 2019-12-11 신라젠(주) 항암 백시니아 바이러스와 관문 저해제 병용 요법
MX2019012431A (es) 2017-04-21 2020-08-03 Ikena Oncology Inc Inhibidores del receptor de hidrocarburos de arilo (ahr) de indol y usos de los mismos.
EP3628070B1 (en) 2017-04-28 2021-09-08 Five Prime Therapeutics, Inc. Cd80 extracellular domain polypeptides for use in increasing central memory t cells
AR111651A1 (es) 2017-04-28 2019-08-07 Novartis Ag Conjugados de anticuerpos que comprenden agonistas del receptor de tipo toll y terapias de combinación
US11066392B2 (en) 2017-05-12 2021-07-20 Bristol-Myers Squibb Company Inhibitors of indoleamine 2,3-dioxygenase and methods of their use
JP2020520923A (ja) 2017-05-17 2020-07-16 ボストン バイオメディカル, インコーポレイテッド がんを処置するための方法
JP7189155B2 (ja) 2017-05-17 2022-12-13 アーカス バイオサイエンシズ インコーポレイティド 癌関連障害の治療のためのキナゾリン-ピラゾール誘導体
WO2018219956A1 (en) 2017-05-29 2018-12-06 Gamamabs Pharma Cancer-associated immunosuppression inhibitor
MX2019012076A (es) 2017-05-30 2019-12-09 Bristol Myers Squibb Co Composiciones que comprenden un anticuerpo anti gen-3 de activacion del linfocito (lag-3) o un anticuerpo anti-lag-3 y un anticuerpo anti muerte celular programada 1 (pd-1) o anti ligando 1 de muerte celular programada (pd-l1).
AU2018277824A1 (en) 2017-05-30 2019-10-17 Bristol-Myers Squibb Company Treatment of LAG-3 positive tumors
MX2019012038A (es) 2017-05-30 2019-11-18 Bristol Myers Squibb Co Composiciones que comprenden una combinacion de un anticuerpo anti gen 3 de activacion del linfocito (lag-3), un inhibidor de la trayectoria del receptor de muerte programada 1 (pd-1), y un agente inmunoterapeutico.
WO2018229715A1 (en) 2017-06-16 2018-12-20 Novartis Ag Compositions comprising anti-cd32b antibodies and methods of use thereof
WO2018235056A1 (en) 2017-06-22 2018-12-27 Novartis Ag IL-1BETA BINDING ANTIBODIES FOR USE IN THE TREATMENT OF CANCER
JP2020524694A (ja) 2017-06-22 2020-08-20 ノバルティス アーゲー がんの処置における使用のためのIL−1β結合性抗体
PE20200717A1 (es) 2017-06-22 2020-07-21 Novartis Ag Moleculas de anticuerpo que se unen a cd73 y usos de las mismas
EP3645037A1 (en) 2017-06-27 2020-05-06 Novartis AG Dosage regimens for anti-tim-3 antibodies and uses thereof
IL271601B2 (en) 2017-06-30 2024-05-01 Bristol Myers Squibb Co Amorphous and crystalline forms of IDO inhibitors
US20200172617A1 (en) 2017-07-20 2020-06-04 Novartis Ag Dosage regimens of anti-lag-3 antibodies and uses thereof
KR20200032180A (ko) 2017-07-28 2020-03-25 브리스톨-마이어스 스큅 컴퍼니 항암제로서의 시클릭 디뉴클레오티드
KR20200051646A (ko) 2017-08-17 2020-05-13 이케나 온콜로지, 인코포레이티드 Ahr 억제제 및 이의 용도
US10953032B2 (en) 2017-08-31 2021-03-23 Bristol-Myers Squibb Company Cyclic dinucleotides as anticancer agents
US10947263B2 (en) 2017-08-31 2021-03-16 Bristol-Myers Squibb Company Cyclic dinucleotides as anticancer agents
JP7316263B2 (ja) 2017-08-31 2023-07-27 ブリストル-マイヤーズ スクイブ カンパニー 抗癌剤としての環状ジヌクレオチド
JP7196160B2 (ja) 2017-09-12 2022-12-26 スミトモ ファーマ オンコロジー, インコーポレイテッド Mcl-1阻害剤アルボシジブを用いた、bcl-2阻害剤に対して非感受性である癌の治療レジメン
MX2020003190A (es) 2017-09-22 2020-11-11 Kymera Therapeutics Inc Degradadores de proteinas y usos de los mismos.
US11358948B2 (en) 2017-09-22 2022-06-14 Kymera Therapeutics, Inc. CRBN ligands and uses thereof
WO2019074822A1 (en) 2017-10-09 2019-04-18 Bristol-Myers Squibb Company INDOLEAMINE 2,3-DIOXYGENASE INHIBITORS AND METHODS OF USE
US11203592B2 (en) 2017-10-09 2021-12-21 Bristol-Myers Squibb Company Inhibitors of indoleamine 2,3-dioxygenase and methods of their use
CN111344297B (zh) 2017-10-10 2023-10-20 百时美施贵宝公司 作为抗癌剂的环二核苷酸
WO2019075090A1 (en) 2017-10-10 2019-04-18 Tilos Therapeutics, Inc. ANTI-LAP ANTIBODIES AND USES THEREOF
KR20200065065A (ko) 2017-10-16 2020-06-08 브리스톨-마이어스 스큅 컴퍼니 항암제로서의 시클릭 디뉴클레오티드
WO2019081983A1 (en) 2017-10-25 2019-05-02 Novartis Ag CD32B TARGETING ANTIBODIES AND METHODS OF USE
KR20200074214A (ko) 2017-11-01 2020-06-24 브리스톨-마이어스 스큅 컴퍼니 암을 치료하는데 사용하기 위한 면역자극 효능작용 항체
JP7167146B2 (ja) 2017-11-06 2022-11-08 ブリストル-マイヤーズ スクイブ カンパニー Hpk1阻害剤として有用なイソフラノン化合物
MX2020004756A (es) 2017-11-16 2020-08-20 Novartis Ag Terapias de combinacion.
BR112020010579A2 (pt) 2017-11-30 2020-11-10 Novartis Ag receptor de antígeno quimérico de alvejamento de bcma e usos do mesmo
JP2021508703A (ja) 2017-12-26 2021-03-11 カイメラ セラピューティクス, インコーポレイテッド Irak分解剤およびそれらの使用
WO2019136112A1 (en) 2018-01-05 2019-07-11 Bristol-Myers Squibb Company Inhibitors of indoleamine 2,3-dioxygenase and methods of their use
CN112218651A (zh) 2018-01-08 2021-01-12 诺华公司 用于与嵌合抗原受体疗法组合的免疫增强rna
US11512080B2 (en) 2018-01-12 2022-11-29 Kymera Therapeutics, Inc. CRBN ligands and uses thereof
CN111886255A (zh) 2018-01-12 2020-11-03 百时美施贵宝公司 抗tim3抗体及其用途
US11485743B2 (en) 2018-01-12 2022-11-01 Kymera Therapeutics, Inc. Protein degraders and uses thereof
US10988477B2 (en) 2018-01-29 2021-04-27 Merck Patent Gmbh GCN2 inhibitors and uses thereof
TW201940481A (zh) 2018-01-29 2019-10-16 美商維泰克斯製藥公司 Gcn2抑制劑及其用途
AU2019215031A1 (en) 2018-01-31 2020-08-20 Novartis Ag Combination therapy using a chimeric antigen receptor
US10519187B2 (en) 2018-02-13 2019-12-31 Bristol-Myers Squibb Company Cyclic dinucleotides as anticancer agents
WO2019160956A1 (en) 2018-02-13 2019-08-22 Novartis Ag Chimeric antigen receptor therapy in combination with il-15r and il15
WO2019165315A1 (en) 2018-02-23 2019-08-29 Syntrix Biosystems Inc. Method for treating cancer using chemokine antagonists alone or in combination
JP7250808B2 (ja) 2018-03-08 2023-04-03 ブリストル-マイヤーズ スクイブ カンパニー 抗がん剤としての環状ジヌクレオチド
KR20200135986A (ko) 2018-03-19 2020-12-04 멀티비르 인코포레이티드 종양 억제인자 유전자 치료 및 cd122/cd132 작용제를 포함하는 암 치료를 위한 방법 및 조성물
CN111971304A (zh) 2018-03-21 2020-11-20 戊瑞治疗有限公司 在酸性pH结合至VISTA的抗体
EP4066851A1 (en) 2018-03-25 2022-10-05 SNIPR Biome ApS. Treating & preventing microbial infections
US10760075B2 (en) 2018-04-30 2020-09-01 Snipr Biome Aps Treating and preventing microbial infections
US20210147547A1 (en) 2018-04-13 2021-05-20 Novartis Ag Dosage Regimens For Anti-Pd-L1 Antibodies And Uses Thereof
CN112292128A (zh) 2018-04-16 2021-01-29 阿瑞斯医疗有限公司 Ep4抑制剂和其用途
WO2019213340A1 (en) 2018-05-03 2019-11-07 Bristol-Myers Squibb Company Uracil derivatives as mer-axl inhibitors
TW202015726A (zh) 2018-05-30 2020-05-01 瑞士商諾華公司 Entpd2抗體、組合療法、及使用該等抗體和組合療法之方法
US20210214459A1 (en) 2018-05-31 2021-07-15 Novartis Ag Antibody molecules to cd73 and uses thereof
BR112020024351A2 (pt) 2018-06-01 2021-02-23 Novartis Ag moléculas de ligação contra bcma e usos das mesmas
US11180531B2 (en) 2018-06-22 2021-11-23 Bicycletx Limited Bicyclic peptide ligands specific for Nectin-4
EP3814347B1 (en) 2018-06-27 2023-05-03 Bristol-Myers Squibb Company Naphthyridinone compounds useful as t cell activators
FI3814348T3 (fi) 2018-06-27 2023-09-22 Bristol Myers Squibb Co Substituoituja naftyridinoniyhdisteitä, jotka ovat käyttökelpoisia t-solun aktivoijina
WO2020010177A1 (en) 2018-07-06 2020-01-09 Kymera Therapeutics, Inc. Tricyclic crbn ligands and uses thereof
EP3820904A2 (en) 2018-07-09 2021-05-19 Five Prime Therapeutics, Inc. Antibodies binding to ilt4
CR20210001A (es) 2018-07-10 2021-04-19 Novartis Ag Derivados de 3-(5-hidroxi-1-oxoisoindolin-2-il)piperidina-2,6-diona y su uso en el tratamiento de trastornos dependientes de la proteina con dedos de zinc 2 de la familia ikaros (1kzf2)
AR116109A1 (es) 2018-07-10 2021-03-31 Novartis Ag Derivados de 3-(5-amino-1-oxoisoindolin-2-il)piperidina-2,6-diona y usos de los mismos
JP2022513421A (ja) 2018-07-11 2022-02-08 ファイブ プライム セラピューティクス, インコーポレイテッド 酸性pHでVISTAと結合する抗体
MX2021000745A (es) 2018-07-20 2021-03-26 Surface Oncology Inc Composiciones anti-cd112r y metodos.
US20210355113A1 (en) 2018-07-23 2021-11-18 Bristol-Myers Squibb Company Inhibitors of indoleamine 2,3-dioxygenase and methods of their use
US20210299126A1 (en) 2018-07-23 2021-09-30 Bristol-Myers Squibb Company Inhibitors of indoleamine 2,3-dioxygenase and methods of their use
WO2020021465A1 (en) 2018-07-25 2020-01-30 Advanced Accelerator Applications (Italy) S.R.L. Method of treatment of neuroendocrine tumors
MX2021000726A (es) 2018-07-26 2021-03-25 Bristol Myers Squibb Co Terapia combinada de gen de activacion de linfocitos 3(lag-3) para el tratamiento del cancer.
US10959986B2 (en) 2018-08-29 2021-03-30 Bristol-Myers Squibb Company Inhibitors of indoleamine 2,3-dioxygenase and methods of their use
US11253525B2 (en) 2018-08-29 2022-02-22 Bristol-Myers Squibb Company Inhibitors of indoleamine 2,3-dioxygenase and methods of their use
CN113164419A (zh) 2018-09-07 2021-07-23 皮克医疗公司 Eif4e抑制剂和其用途
CN113164780A (zh) 2018-10-10 2021-07-23 泰洛斯治疗公司 抗lap抗体变体及其用途
KR20210080437A (ko) 2018-10-19 2021-06-30 브리스톨-마이어스 스큅 컴퍼니 흑색종을 위한 조합 요법
WO2020089811A1 (en) 2018-10-31 2020-05-07 Novartis Ag Dc-sign antibody drug conjugates
CA3119773A1 (en) 2018-11-30 2020-06-04 Kymera Therapeutics, Inc. Irak degraders and uses thereof
EP3890749A4 (en) 2018-12-04 2022-08-03 Sumitomo Dainippon Pharma Oncology, Inc. CDK9 INHIBITORS AND POLYMORPHS THEREOF FOR USE AS CANCER TREATMENT AGENT
EP3670659A1 (en) 2018-12-20 2020-06-24 Abivax Biomarkers, and uses in treatment of viral infections, inflammations, or cancer
KR20210106437A (ko) 2018-12-20 2021-08-30 노파르티스 아게 3-(1-옥소이소인돌린-2-일)피페리딘-2,6-디온 유도체를 포함하는 투약 요법 및 약학적 조합물
JP2022516850A (ja) 2018-12-21 2022-03-03 ノバルティス アーゲー 骨髄異形成症候群の治療又は予防におけるIL-1β抗体の使用
WO2020128637A1 (en) 2018-12-21 2020-06-25 Novartis Ag Use of il-1 binding antibodies in the treatment of a msi-h cancer
WO2020128613A1 (en) 2018-12-21 2020-06-25 Novartis Ag Use of il-1beta binding antibodies
AU2019409139A1 (en) 2018-12-21 2021-06-03 Novartis Ag Use of IL-1β binding antibodies
KR20210146290A (ko) 2019-02-12 2021-12-03 스미토모 다이니폰 파마 온콜로지, 인크. 헤테로시클릭 단백질 키나제 억제제를 포함하는 제제
EP3924055B1 (en) 2019-02-15 2024-04-03 Novartis AG Substituted 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof
US20220144807A1 (en) 2019-02-15 2022-05-12 Novartis Ag 3-(1-oxo-5-(piperidin-4-yl)isoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof
WO2020187998A1 (en) 2019-03-19 2020-09-24 Fundació Privada Institut D'investigació Oncològica De Vall Hebron Combination therapy with omomyc and an antibody binding pd-1 or ctla-4 for the treatment of cancer
US11793802B2 (en) 2019-03-20 2023-10-24 Sumitomo Pharma Oncology, Inc. Treatment of acute myeloid leukemia (AML) with venetoclax failure
WO2020198077A1 (en) 2019-03-22 2020-10-01 Sumitomo Dainippon Pharma Oncology, Inc. Compositions comprising pkm2 modulators and methods of treatment using the same
AU2020253990A1 (en) 2019-04-02 2021-10-28 Bicycletx Limited Bicycle toxin conjugates and uses thereof
TW202106676A (zh) 2019-04-05 2021-02-16 美商凱麥拉醫療公司 Stat降解劑及其用途
GB201906118D0 (en) 2019-05-01 2019-06-12 Immutep S A Anti-LAG-3 binding molecules
US12012374B2 (en) 2019-05-13 2024-06-18 Bristol-Myers Squibb Company Agonists of ROR GAMMAt
WO2020231766A1 (en) 2019-05-13 2020-11-19 Bristol-Myers Squibb Company AGONISTS OF ROR GAMMAt
WO2020243568A1 (en) 2019-05-30 2020-12-03 Bristol-Myers Squibb Company Methods of identifying a subject suitable for an immuno-oncology (i-o) therapy
CN114174538A (zh) 2019-05-30 2022-03-11 百时美施贵宝公司 适合于免疫肿瘤学疗法的多肿瘤基因特征
KR20220016157A (ko) 2019-05-30 2022-02-08 브리스톨-마이어스 스큅 컴퍼니 세포 국재화 시그너쳐 및 조합 요법
CN114502540A (zh) 2019-05-31 2022-05-13 医肯纳肿瘤学公司 Tead抑制剂和其用途
CN114302878A (zh) 2019-07-03 2022-04-08 大日本住友制药肿瘤公司 酪氨酸激酶非受体1(tnk1)抑制剂及其用途
CN110320352A (zh) * 2019-07-25 2019-10-11 上海轩锋生物科技有限公司 基于抗体依赖的细胞介导细胞毒性的抗体效价检测方法
WO2021024020A1 (en) 2019-08-06 2021-02-11 Astellas Pharma Inc. Combination therapy involving antibodies against claudin 18.2 and immune checkpoint inhibitors for treatment of cancer
US20220306630A1 (en) 2019-08-06 2022-09-29 Bristol-Myers Squibb Company AGONISTS OF ROR GAMMAt
AR119821A1 (es) 2019-08-28 2022-01-12 Bristol Myers Squibb Co Compuestos de piridopirimidinonilo sustituidos útiles como activadores de células t
WO2021050964A1 (en) 2019-09-13 2021-03-18 Nimbus Saturn, Inc. Hpk1 antagonists and uses thereof
CN114502590A (zh) 2019-09-18 2022-05-13 诺华股份有限公司 Entpd2抗体、组合疗法、以及使用这些抗体和组合疗法的方法
JP2022548292A (ja) 2019-09-19 2022-11-17 ブリストル-マイヤーズ スクイブ カンパニー 酸性pHでVISTAと結合する抗体
JP2022549273A (ja) 2019-09-22 2022-11-24 ブリストル-マイヤーズ スクイブ カンパニー Lag-3アンタゴニスト治療のための定量的空間プロファイリング
BR112022007376A2 (pt) 2019-10-21 2022-07-05 Novartis Ag Terapias de combinação com venetoclax e inibidores de tim-3
WO2021079195A1 (en) 2019-10-21 2021-04-29 Novartis Ag Tim-3 inhibitors and uses thereof
WO2021092220A1 (en) 2019-11-06 2021-05-14 Bristol-Myers Squibb Company Methods of identifying a subject with a tumor suitable for a checkpoint inhibitor therapy
WO2021092221A1 (en) 2019-11-06 2021-05-14 Bristol-Myers Squibb Company Methods of identifying a subject with a tumor suitable for a checkpoint inhibitor therapy
KR20220093349A (ko) 2019-11-08 2022-07-05 브리스톨-마이어스 스큅 컴퍼니 흑색종에 대한 lag-3 길항제 요법
JP2023503052A (ja) 2019-11-19 2023-01-26 ブリストル-マイヤーズ スクイブ カンパニー Heliosタンパク質の阻害剤として有用な化合物
IL293357A (en) 2019-11-26 2022-07-01 Bristol Myers Squibb Co Salts/crystals of (r)-n-(4-chlorophenyl)-2-((1s,4s)-4-(6-fluoroquinolin-4-yl)cyclohexyl)propanamide
EP4065582A1 (en) 2019-11-26 2022-10-05 Ikena Oncology, Inc. Polymorphic carbazole derivatives and uses thereof
WO2021113644A1 (en) 2019-12-05 2021-06-10 Multivir Inc. Combinations comprising a cd8+ t cell enhancer, an immune checkpoint inhibitor and radiotherapy for targeted and abscopal effects for the treatment of cancer
WO2021127283A2 (en) 2019-12-17 2021-06-24 Kymera Therapeutics, Inc. Irak degraders and uses thereof
US11779578B2 (en) 2019-12-17 2023-10-10 Kymera Therapeutics, Inc. IRAK degraders and uses thereof
WO2021123996A1 (en) 2019-12-20 2021-06-24 Novartis Ag Uses of anti-tgf-beta antibodies and checkpoint inhibitors for the treatment of proliferative diseases
CA3162502A1 (en) 2019-12-23 2021-07-01 Yi Zhang Smarca degraders and uses thereof
IL294269A (en) 2019-12-23 2022-08-01 Bristol Myers Squibb Co Substitute quinolinyl piperazine compounds are useful as t-cell activators
BR112022012179A2 (pt) 2019-12-23 2022-09-06 Bristol Myers Squibb Co Compostos de quinazolina substituída úteis como ativadores de célula t
KR20220120624A (ko) 2019-12-23 2022-08-30 브리스톨-마이어스 스큅 컴퍼니 T 세포 활성화제로서 유용한 치환된 피페라진 유도체
AR120823A1 (es) 2019-12-23 2022-03-23 Bristol Myers Squibb Co Compuestos bicíclicos sustituidos útiles como activadores de células t
CN114846015A (zh) 2019-12-23 2022-08-02 百时美施贵宝公司 用作t细胞激活剂的经取代的杂芳基化合物
EP4087874A1 (en) 2020-01-06 2022-11-16 HiFiBiO (HK) Limited Anti-tnfr2 antibody and uses thereof
MX2022008421A (es) 2020-01-07 2022-09-23 Hifibio Hk Ltd Anticuerpo anti-galectina-9 y usos del mismo.
AR121047A1 (es) 2020-01-15 2022-04-13 Blueprint Medicines Corp Inhibidores de map4k1
JP2023510393A (ja) 2020-01-17 2023-03-13 ノバルティス アーゲー 骨髄異形成症候群または慢性骨髄単球性白血病の処置に使用するためのtim-3阻害剤と低メチル化剤とを含む組合せ
JP2023514152A (ja) 2020-02-06 2023-04-05 ブリストル-マイヤーズ スクイブ カンパニー Il-10およびその使用
KR20220164706A (ko) 2020-03-03 2022-12-13 피아이씨 테라퓨틱스 인코포레이티드 Eif4e 억제제 및 이의 용도
MX2022011534A (es) 2020-03-19 2022-10-13 Arcus Biosciences Inc Compuestos de tetralina y tetrahidroquinolina como inhibidores de hif-2alfa.
JP2023518423A (ja) 2020-03-19 2023-05-01 カイメラ セラピューティクス, インコーポレイテッド Mdm2分解剤およびそれらの使用
TW202140441A (zh) 2020-03-23 2021-11-01 美商必治妥美雅史谷比公司 經取代之側氧基異吲哚啉化合物
EP4132971A1 (en) 2020-04-09 2023-02-15 Merck Sharp & Dohme LLC Affinity matured anti-lap antibodies and uses thereof
IL298507A (en) 2020-05-28 2023-01-01 Immutep Sas Cancer treatment
JP2023528036A (ja) 2020-06-02 2023-07-03 アーカス バイオサイエンシズ インコーポレイティド Tigitに対する抗体
WO2021245071A1 (en) 2020-06-03 2021-12-09 Mv Biotherapeutics Sa Combination of an atp-hydrolyzing enzyme and an immune checkpoint modulator and uses thereof
TW202210483A (zh) 2020-06-03 2022-03-16 美商凱麥拉醫療公司 Irak降解劑之結晶型
WO2021258010A1 (en) 2020-06-19 2021-12-23 Gossamer Bio Services, Inc. Oxime compounds useful as t cell activators
CN115916199A (zh) 2020-06-23 2023-04-04 诺华股份有限公司 包含3-(1-氧代异吲哚啉-2-基)哌啶-2,6-二酮衍生物的给药方案
AU2021306613A1 (en) 2020-07-07 2023-02-02 BioNTech SE Therapeutic RNA for HPV-positive cancer
US11857535B2 (en) 2020-07-30 2024-01-02 Kymera Therapeutics, Inc. Methods of treating mutant lymphomas
US20230271940A1 (en) 2020-08-03 2023-08-31 Novartis Ag Heteroaryl substituted 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof
WO2022033419A2 (en) 2020-08-10 2022-02-17 Shanghai Xbh Biotechnology Co., Ltd. Compositions and methods for treating autoimmune diseases and cancers by targeting igsf8
EP4196792A1 (en) 2020-08-17 2023-06-21 BicycleTX Limited Bicycle conjugates specific for nectin-4 and uses thereof
AU2021331476A1 (en) 2020-08-28 2023-05-04 Bristol-Myers Squibb Company Lag-3 antagonist therapy for hepatocellular carcinoma
US20230303700A1 (en) 2020-08-31 2023-09-28 Bristol-Myers Squibb Company Cell localization signature and immunotherapy
WO2022043557A1 (en) 2020-08-31 2022-03-03 Advanced Accelerator Applications International Sa Method of treating psma-expressing cancers
US20230338587A1 (en) 2020-08-31 2023-10-26 Advanced Accelerator Applications International Sa Method of treating psma-expressing cancers
AU2021341521A1 (en) 2020-09-14 2023-03-30 Boehringer Ingelheim International Gmbh Heterologous prime boost vaccine
CA3198456A1 (en) 2020-10-14 2022-04-21 Five Prime Therapeutics, Inc. Anti-c-c chemokine receptor 8 (ccr8) antibodies and methods of use thereof
JP2023548051A (ja) 2020-10-23 2023-11-15 ブリストル-マイヤーズ スクイブ カンパニー 肺がんのためのlag-3アンタゴニスト療法
KR20230104651A (ko) 2020-11-06 2023-07-10 노파르티스 아게 Cd19 결합 분자 및 이의 용도
WO2022120353A1 (en) 2020-12-02 2022-06-09 Ikena Oncology, Inc. Tead inhibitors and uses thereof
KR20230131189A (ko) 2020-12-02 2023-09-12 이케나 온콜로지, 인코포레이티드 Tead 억제제 및 이의 용도
WO2022120179A1 (en) 2020-12-03 2022-06-09 Bristol-Myers Squibb Company Multi-tumor gene signatures and uses thereof
TW202237119A (zh) 2020-12-10 2022-10-01 美商住友製藥腫瘤公司 Alk﹘5抑制劑和彼之用途
CN116964050A (zh) 2020-12-16 2023-10-27 戈萨默生物服务公司 可用作t细胞激活剂的化合物
WO2022135666A1 (en) 2020-12-21 2022-06-30 BioNTech SE Treatment schedule for cytokine proteins
WO2022135667A1 (en) 2020-12-21 2022-06-30 BioNTech SE Therapeutic rna for treating cancer
TW202245808A (zh) 2020-12-21 2022-12-01 德商拜恩迪克公司 用於治療癌症之治療性rna
EP4267172A1 (en) 2020-12-28 2023-11-01 Bristol-Myers Squibb Company Subcutaneous administration of pd1/pd-l1 antibodies
EP4267105A1 (en) 2020-12-28 2023-11-01 Bristol-Myers Squibb Company Antibody compositions and methods of use thereof
EP4274597A1 (en) 2021-01-11 2023-11-15 BicycleTX Limited Methods for treating cancer
US20230091528A1 (en) 2021-02-02 2023-03-23 Liminal Biosciences Limited Gpr84 antagonists and uses thereof
AU2022216810A1 (en) 2021-02-02 2023-08-24 Liminal Biosciences Limited Gpr84 antagonists and uses thereof
WO2022169921A1 (en) 2021-02-04 2022-08-11 Bristol-Myers Squibb Company Benzofuran compounds as sting agonists
CR20230382A (es) 2021-02-12 2023-09-06 Hoffmann La Roche Derivados de tetrahidroazepina bicíclicos para el tratamiento del cáncer
AU2022220869A1 (en) 2021-02-15 2023-08-24 Kymera Therapeutics, Inc. Irak4 degraders and uses thereof
WO2022187856A1 (en) 2021-03-05 2022-09-09 Nimbus Saturn, Inc. Hpk1 antagonists and uses thereof
WO2022192145A1 (en) 2021-03-08 2022-09-15 Blueprint Medicines Corporation Map4k1 inhibitors
US11918582B2 (en) 2021-03-15 2024-03-05 Rapt Therapeutics, Inc. Pyrazole pyrimidine compounds and uses thereof
IL307262A (en) 2021-03-29 2023-11-01 Juno Therapeutics Inc METHODS FOR DOSAGE AND THERAPY IN COMBINATION OF CHECKPOINT INHIBITOR AND CAR T CELL THERAPY
IL307338A (en) 2021-04-05 2023-11-01 Bristol Myers Squibb Co Pyridinyl substituted oxisoisoindoline compounds for cancer therapy
US11718601B2 (en) 2021-04-06 2023-08-08 Bristol-Myers Squibb Company Pyridinyl substituted oxoisoindoline compounds
TW202304979A (zh) 2021-04-07 2023-02-01 瑞士商諾華公司 抗TGFβ抗體及其他治療劑用於治療增殖性疾病之用途
TW202309022A (zh) 2021-04-13 2023-03-01 美商努法倫特公司 用於治療具egfr突變之癌症之胺基取代雜環
JP2024514879A (ja) 2021-04-16 2024-04-03 イケナ オンコロジー, インコーポレイテッド Mek阻害剤及びその使用
WO2022240741A1 (en) 2021-05-12 2022-11-17 Dana-Farber Cancer Institute, Inc. Lag3 and gal3 inhibitory agents, xbp1, cs1, and cd138 peptides, and methods of use thereof
AR125874A1 (es) 2021-05-18 2023-08-23 Novartis Ag Terapias de combinación
CN117337288A (zh) 2021-05-21 2024-01-02 艾库斯生物科学有限公司 Axl抑制剂化合物
TW202313602A (zh) 2021-05-21 2023-04-01 美商阿克思生物科學有限公司 Axl化合物
GB202108718D0 (en) 2021-06-18 2021-08-04 Immutep Sas Triple combination therapy
WO2023285552A1 (en) 2021-07-13 2023-01-19 BioNTech SE Multispecific binding agents against cd40 and cd137 in combination therapy for cancer
AR126442A1 (es) 2021-07-14 2023-10-11 Blueprint Medicines Corp Inhibidores de map4k1
CN117940406A (zh) 2021-07-15 2024-04-26 缆图药品公司 Map4k1抑制剂
US20230134932A1 (en) 2021-08-25 2023-05-04 PIC Therapeutics, Inc. Eif4e inhibitors and uses thereof
WO2023028235A1 (en) 2021-08-25 2023-03-02 PIC Therapeutics, Inc. Eif4e inhibitors and uses thereof
TW202333802A (zh) 2021-10-11 2023-09-01 德商拜恩迪克公司 用於肺癌之治療性rna(二)
CA3224890A1 (en) 2021-10-29 2023-05-04 Bristol-Myers Squibb Company Lag-3 antagonist therapy for hematological cancer
US20230159466A1 (en) 2021-10-29 2023-05-25 Arcus Biosciences, Inc. Inhibitors of hif-2alpha and methods of use thereof
WO2023114984A1 (en) 2021-12-17 2023-06-22 Ikena Oncology, Inc. Tead inhibitors and uses thereof
WO2023122772A1 (en) 2021-12-22 2023-06-29 Gossamer Bio Services, Inc. Oxime derivatives useful as t cell activators
WO2023122778A1 (en) 2021-12-22 2023-06-29 Gossamer Bio Services, Inc. Pyridazinone derivatives useful as t cell activators
WO2023122777A1 (en) 2021-12-22 2023-06-29 Gossamer Bio Services, Inc. Oxime derivatives useful as t cell activators
WO2023147371A1 (en) 2022-01-26 2023-08-03 Bristol-Myers Squibb Company Combination therapy for hepatocellular carcinoma
WO2023150186A1 (en) 2022-02-01 2023-08-10 Arvinas Operations, Inc. Dgk targeting compounds and uses thereof
WO2023152335A1 (en) 2022-02-11 2023-08-17 Immutep S.A.S. Treatment of cancer
WO2023164638A1 (en) 2022-02-25 2023-08-31 Bristol-Myers Squibb Company Combination therapy for colorectal carcinoma
WO2023168404A1 (en) 2022-03-04 2023-09-07 Bristol-Myers Squibb Company Methods of treating a tumor
WO2023170606A1 (en) 2022-03-08 2023-09-14 Alentis Therapeutics Ag Use of anti-claudin-1 antibodies to increase t cell availability
WO2023173057A1 (en) 2022-03-10 2023-09-14 Ikena Oncology, Inc. Mek inhibitors and uses thereof
WO2023173053A1 (en) 2022-03-10 2023-09-14 Ikena Oncology, Inc. Mek inhibitors and uses thereof
WO2023178192A1 (en) 2022-03-15 2023-09-21 Compugen Ltd. Il-18bp antagonist antibodies and their use in monotherapy and combination therapy in the treatment of cancer
WO2023178329A1 (en) 2022-03-18 2023-09-21 Bristol-Myers Squibb Company Methods of isolating polypeptides
WO2023211889A1 (en) 2022-04-25 2023-11-02 Ikena Oncology, Inc. Polymorphic compounds and uses thereof
WO2023214325A1 (en) 2022-05-05 2023-11-09 Novartis Ag Pyrazolopyrimidine derivatives and uses thereof as tet2 inhibitors
TW202404581A (zh) 2022-05-25 2024-02-01 美商醫肯納腫瘤學公司 Mek抑制劑及其用途
WO2023235847A1 (en) 2022-06-02 2023-12-07 Bristol-Myers Squibb Company Antibody compositions and methods of use thereof
US20240124490A1 (en) 2022-07-15 2024-04-18 Arcus Biosciences, Inc. Inhibitors of hpk1 and methods of use thereof
WO2024020034A1 (en) 2022-07-20 2024-01-25 Arcus Biosciences, Inc. Cbl-b inhibitors and methods of use thereof
WO2024028365A1 (en) 2022-08-02 2024-02-08 Liminal Biosciences Limited Substituted pyridone gpr84 antagonists and uses thereof
WO2024028364A1 (en) 2022-08-02 2024-02-08 Liminal Biosciences Limited Aryl-triazolyl and related gpr84 antagonists and uses thereof
WO2024028363A1 (en) 2022-08-02 2024-02-08 Liminal Biosciences Limited Heteroaryl carboxamide and related gpr84 antagonists and uses thereof
WO2024036100A1 (en) 2022-08-08 2024-02-15 Bristol-Myers Squibb Company Substituted tetrazolyl compounds useful as t cell activators
WO2024036101A1 (en) 2022-08-09 2024-02-15 Bristol-Myers Squibb Company Tertiary amine substituted bicyclic compounds useful as t cell activators
WO2024033458A1 (en) 2022-08-11 2024-02-15 F. Hoffmann-La Roche Ag Bicyclic tetrahydroazepine derivatives
WO2024033389A1 (en) 2022-08-11 2024-02-15 F. Hoffmann-La Roche Ag Bicyclic tetrahydrothiazepine derivatives
WO2024033388A1 (en) 2022-08-11 2024-02-15 F. Hoffmann-La Roche Ag Bicyclic tetrahydrothiazepine derivatives
WO2024033457A1 (en) 2022-08-11 2024-02-15 F. Hoffmann-La Roche Ag Bicyclic tetrahydrothiazepine derivatives
WO2024059142A1 (en) 2022-09-14 2024-03-21 Arcus Biosciences, Inc. Dispersions of etrumadenant
WO2024081385A1 (en) 2022-10-14 2024-04-18 Arcus Biosciences, Inc. Hpk1 inhibitors and methods of use thereof
WO2024086718A1 (en) 2022-10-20 2024-04-25 Arcus Biosciences, Inc. Lyophilized formulations of cd73 compounds
WO2024116140A1 (en) 2022-12-01 2024-06-06 Medimmune Limited Combination therapy for treatment of cancer comprising anti-pd-l1 and anti-cd73 antibodies
WO2024126457A1 (en) 2022-12-14 2024-06-20 Astellas Pharma Europe Bv Combination therapy involving bispecific binding agents binding to cldn18.2 and cd3 and immune checkpoint inhibitors

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1265149A (zh) * 1997-07-25 2000-08-30 古斯塔夫鲁西研究院 Mhc-11-类配体作为疫苗佐剂以及lag-3用于癌症治疗的应用

Family Cites Families (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA1341281C (en) 1986-07-09 2001-08-07 Hubert J.P. Schoemaker Immunotherapy of tumor with monoclonal antibody against the 17-1a antigen
US5785973A (en) * 1988-02-01 1998-07-28 Praxis Biologics, Inc. Synthetic peptides representing a T-cell epitope as a carrier molecule for conjugate vaccines
AU642403B2 (en) * 1989-02-17 1993-10-21 Coselco Mimotopes Pty Ltd Method for the use and synthesis of peptides
US5976877A (en) 1990-01-08 1999-11-02 Institut National De La Sante Et De La Recherche Medicale (Inserm) Proteins produced by human lymphocytes DNA sequence encoding these proteins and their pharmaceutical and biological uses
FR2656800B1 (fr) 1990-01-08 1992-05-15 Roussy Inst Gustave Nouvelles proteines produits par les lymphocytes humains, sequence d'adn codant pour ces proteines et applications pharmaceutiques et biologiques.
US7294712B2 (en) 1990-06-04 2007-11-13 Aventis Pharma S.A. Nucleotide sequences coding for variable regions of β chains of human T lymphocyte receptors, corresponding peptide segments and the diagnostic and therapeutic uses
US6596536B1 (en) 1991-02-08 2003-07-22 Aventis Pharma S.A. Nucleotide sequences coding for variable regions of the alpha chains of human T lymphocyte receptors, corresponding peptide segments and the diagnostic and therapeutic uses
CA2079879C (fr) 1991-02-08 2007-11-06 Thierry Hercend Sequences nucleotidiques codant pour des regions variables de chaines alpha des recepteurs des lymphocytes humains ainsi que leurs applications
CA2079881C (fr) 1991-02-12 2007-11-06 Thierry Hercend Sequences nucleotidiques codant pour des regions variables de chaines .beta. des recepteurs des lymphocytes t humains, segments peptidiques correspondants et les applications diagnostiques et therapeutiques
DK0758383T3 (da) 1994-05-06 2007-05-29 Roussy Inst Gustave Oplöselige polypeptidfraktioner af LAG-3-proteinet; fremgangsmåde til fremstilling; terapeutisk sammensætning; antiidiotypisk antistof
AU6267896A (en) * 1995-06-07 1996-12-30 Imclone Systems Incorporated Antibody and antibody fragments for inhibiting the growth oftumors
US5840839A (en) * 1996-02-09 1998-11-24 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Alternative open reading frame DNA of a normal gene and a novel human cancer antigen encoded therein
US6277368B1 (en) * 1996-07-25 2001-08-21 The Regents Of The University Of California Cancer immunotherapy using autologous tumor cells combined with cells expressing a membrane cytokine
CA2273080C (fr) * 1996-11-28 2004-11-09 Institut Gustave Roussy Mutants de la proteine lag-3, leur expression et utilisation
IL130168A (en) * 1996-11-29 2006-09-05 Serono Lab Genetically engineered cells containing LAG-3-expressing DNA and their use
FR2777890B1 (fr) 1998-04-22 2000-12-29 Roussy Inst Gustave Composes peptidiques d'hsp70 utiles dans l'immunotherapie du cancer
FR2795415B1 (fr) 1999-06-28 2003-09-05 Roussy Inst Gustave Compose peptidique derive d'une orf decalee du gene ice
AT409086B (de) * 1999-11-16 2002-05-27 Igeneon Krebs Immuntherapie Neue verwendung von antikörpern als impfstoffe
EP1276468A1 (fr) 2000-04-26 2003-01-22 Biovector Therapeutics S.A. Utilisation de vecteurs particulaires dans l' immunomodulation
DK1294401T3 (da) * 2000-06-29 2007-10-08 Merck Patent Gmbh Forbedring af antistof/cytokin-fusionsproteinmedierede immunresponser ved kombineret behandling med immuncytokin-optagelsesforberende midler
EP1295895B1 (en) 2001-09-19 2011-08-10 Institut Gustave Roussy Peptides and proteins binding to glu-pro motifs, therapeutical compositions containing the same and applications thereof
JP2007508319A (ja) * 2003-10-10 2007-04-05 パウダージェクト ワクチンズ,インコーポレーテッド 方法
FR2868781B1 (fr) 2004-04-13 2008-02-22 Immutep Composition de vaccin comprenant un ligand cmh de classe ii couple a un antigene, procede de preparation et utilisations
JP2006124383A (ja) 2004-09-30 2006-05-18 Kobayashi Pharmaceut Co Ltd 樹状細胞活性化剤
JP2006141346A (ja) 2004-11-24 2006-06-08 Kobayashi Pharmaceut Co Ltd 樹状細胞活性化剤
JP2009504787A (ja) * 2005-08-19 2009-02-05 シーラス コーポレイション 抗体によって媒介される免疫応答の増強
AU2008266951B2 (en) 2007-06-18 2013-12-12 Merck Sharp & Dohme B.V. Antibodies to human programmed death receptor PD-1
US8425897B2 (en) 2007-08-30 2013-04-23 Immutep S.A. Compositions containing LAG-3 and cells that secrete GM-CSF and methods of use
EP2044949A1 (en) 2007-10-05 2009-04-08 Immutep Use of recombinant lag-3 or the derivatives thereof for eliciting monocyte immune response
CN104470949A (zh) 2012-05-15 2015-03-25 百时美施贵宝公司 通过破坏pd-1/pd-l1信号传输的免疫治疗
GB201322626D0 (en) 2013-12-19 2014-02-05 Immutep S A Combined preparations for the treatment of cancer
GB201500374D0 (en) 2015-01-09 2015-02-25 Immutep S A Combined preparations for the treatment of cancer

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1265149A (zh) * 1997-07-25 2000-08-30 古斯塔夫鲁西研究院 Mhc-11-类配体作为疫苗佐剂以及lag-3用于癌症治疗的应用

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
CHIARA CASATI, ET AL.: "Soluble Human LAG-3 Molecule Amplifies the In vitro Generation of Type 1 Tumor-Specific Immunity", 《CANCER RESEARCH》 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10954246B2 (en) 2017-04-13 2021-03-23 Taizhou Eoc Pharma Co., Ltd. Compound of EOC315 Mod.I crystal form and preparation method thereof
CN110950966A (zh) * 2019-12-13 2020-04-03 启辰生生物科技(珠海)有限公司 融合蛋白、编码核酸和细胞及用途

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