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项与 Anti-TM4SF1-CAR-T-cell therapy (Shanghai Biomed-union Biotechnology) 相关的临床试验A Clinical Study on the Safety and Efficacy of Chimeric Antigen Receptor T-cell Therapy for the TM4SF1- and EpCAM-positive Recurrent/Refractory Solid Tumors
Transmembrane 4 L Six Family Member 1 (TM4SF1) and Epithelial cell adhesion molecule (EpCAM) are both highly expressed in many epithelial-derived solid tumors.
The Chimeric Antigen Receptor T-cells (CAR-T) that target TM4SF1 or EpCAM have been generated respectively in our good manufacturing practices (GMP) facility and their anti-tumor effects have been demonstrated in multiple in vitro and in vivo studies.
Clinical studies are proposed here to evaluate the anti-tumor activity of these cell therapy products for treatment of patients with TM4SF1 or EpCAM positive tumors. In this study, the safety, tolerance, and preliminary efficacy of CART-TM4SF1 and CART-EpCAM cells will be examined inpatients with refractory/recurrent advanced pancreatic cancer, colorectal cancer, gastric cancer or lung cancer. And 9 patients for each cancer will be evaluated.
Clinical and immunological responses will be evaluated about 30 days and last up to 2 years after CAR-T cell infusion.
100 项与 Anti-TM4SF1-CAR-T-cell therapy (Shanghai Biomed-union Biotechnology) 相关的临床结果
100 项与 Anti-TM4SF1-CAR-T-cell therapy (Shanghai Biomed-union Biotechnology) 相关的转化医学
100 项与 Anti-TM4SF1-CAR-T-cell therapy (Shanghai Biomed-union Biotechnology) 相关的专利(医药)
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项与 Anti-TM4SF1-CAR-T-cell therapy (Shanghai Biomed-union Biotechnology) 相关的新闻(医药)Transmembrane 4 L six family 1 (TM4SF1)是 L6 家族的成员,最初于1986年被发现,包含202个氨基酸,分子量约22kDa,结构包括四个跨膜结构域(TM1-4)、N-端和C-端胞内结构域、两个胞外结构域。胞外结构域中稍短的环为EC1,位于TM1和TM2之间;稍长的环为EC2,位于TM3和TM4之间,包含一个三α环(A,B和E)和一个变化结构域[1]TM4SF1与四次跨膜蛋白(tetraspanins)、整合素、受体酪氨酸激酶和其他蛋白相互作用,形成富含四跨膜蛋白的微域。这种相互作用影响了细胞的pro-migratory活动,因此它在癌症的发生和进展中起着重要作用。差异化表达和独特的内化途径TM4SF1在正常人和小鼠组织中呈低或中水平表达,而在许多恶性肿瘤中过表达,包括胶质瘤、恶性黑色素瘤、以及肝脏、前列腺、乳腺、胰腺、膀胱、结肠、肺、胃、卵巢和甲状腺癌。除肿瘤细胞外,TM4SF1在肿瘤内皮细胞中也呈高表达。TM4SF1过表达能够显著增加上皮间质转化(EMT),进而促进癌细胞的生长、迁移和侵袭,是几种癌症的独立预后指标和生物标志物,此外,TM4SF1还能够促进耐药,这些特点使TM4SF1成为癌症免疫疗法的潜力靶标。TM4SF1促进癌细胞的生长及转移[1]加之TM3SF1具有通过微管内化到细胞核的特点,其差异表达和独特的内化途径使TM3SF1可被用作开发具有双重作用机制的ADC药物。TM4SF1 ADC比较值得关注的是Angiex的TM4SF1 ADC药物AGX101,于去年9月提交IND。AGX101通过不可裂解linker和工程化半胱氨酸定点偶联技术连接美登素载荷,DAR值为2,是基于其核递送平台ND-ADCs™开发的首个管线。AGX101的独特之处在于具有从细胞膜到细胞核的新型内化途径,抗TM4SF1抗体能够内化入核,进而提高疗效并避免部分耐药机制。体外研究显示,AGX101在内皮细胞和肿瘤细胞中均有显著的皮摩尔抑制效果。体内研究中同样具有显著的抗肿瘤疗效。TM4SF1 CAR-T就国内而言,科棋药业已经申报TM4SF1 CAR-T临床,治疗复发/难治性晚期实体瘤。在早前与第十人民医院合作开展了一项名为“嵌合抗原受体T细胞治疗TM4SF1阳性的复发/难治性实体瘤安全性和有效性的初步临床研究”。据公开资料显示,一位进行直肠癌根治性手术后复发的患者,在参加了科棋药业针对L6靶点的CAR-T细胞治疗临床研究,回输五天后,久治不愈的胸壁溃疡痊愈,原来比较坚硬的癌周组织也变软了,疼痛基本消失。参考:[1]https://doi.org/10.3389/fmolb.2020.00202细胞系产品查询投稿丨商务合作加入交流群往期推荐2023全球医药研发全景展望2022国产PD(L)1市场概览2023第一季度裁员盘点点击下方“药研网”,关注更多精彩内容
100 项与 Anti-TM4SF1-CAR-T-cell therapy (Shanghai Biomed-union Biotechnology) 相关的药物交易