Unit of Molecular Therapies, Department of Experimental Oncology & Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, via Amadeo 42, 20133 Milan, Italy.
Future Oncol. 2013 Apr;9(4):527-39. doi: 10.2217/fon.12.203.
T cells are the most potent cells of the immune system; however, they fail in the immunosurveillance of tumors. In previous decades, scientists began studying methods to take advantage of T-cell potency in cancer therapy by redirecting them against tumors independently from the T-cell receptor-defined specificity. Among different approaches, the most promising are the use of bispecific antibodies and T-cell engineering to create chimeric antigen receptors. Bispecific antibodies, by simultaneously recognizing target antigen and an activating receptor on the surface of an immune effector cell, offer an opportunity to redirect immune effector cells to kill cancer cells. The other approach is the generation of chimeric antigen receptors by fusing extracellular antibodies to intracellular signaling domains. Chimeric antigen receptor-engineered T cells are able to specifically kill tumor cells in a MHC-independent way. The efficacy of these reagents in different formats has been clinically validated and will be presented here.
T 细胞是免疫系统中最有效的细胞；然而，它们在肿瘤的免疫监视中失败了。在过去的几十年中，科学家们开始研究利用 T 细胞在癌症治疗中的效力的方法，方法是将它们与 T 细胞受体定义的特异性独立地针对肿瘤进行重定向。在不同的方法中，最有前途的方法是使用双特异性抗体和 T 细胞工程来创建嵌合抗原受体。双特异性抗体通过同时识别靶抗原和免疫效应细胞表面的激活受体，为将免疫效应细胞重定向以杀死癌细胞提供了机会。另一种方法是通过将细胞外抗体融合到细胞内信号域来产生嵌合抗原受体。嵌合抗原受体工程 T 细胞能够以 MHC 非依赖性的方式特异性杀死肿瘤细胞。这些试剂以不同形式的疗效已在临床上得到验证，并将在此介绍。
