设计嵌合抗原受体有效安全的对抗靶向肿瘤 - 中国病毒学论坛|我们一直在坚持！

The adoptive transfer of T cells engineered to express artificial chimeric antigen receptors CARs) that target a tumor cell surface molecule has emerged as an exciting new approach for cancer immunotherapy. Clinical trials in patients with advanced B cell malignancies treated with CD19-specific CAR-modified T cells (CAR-T) have shown impressive antitumor efficacy, leading to optimism that this approach will be useful for treating common solid tumors. Because CAR-T cells recognize tumor cells independent of their expression of human leukocyte antigen (HLA) molecules, tumors that escape conventional T cells by downregulating HLA and/or mutating components of the antigen processing machinery can be eliminated. The ability to introduce or delete additional genes in T cells has the potential to provide therapeutic cell products with novel attributes that overcome impediments to immune mediated tumor elimination in immunosuppressive tumor microenvironments. This review will discuss recent concepts in the development of effective and safe synthetic CARs for adoptive T cell therapy (ACT).

靶向肿瘤细胞表面的人工嵌合抗原受体修饰的T细胞的过继移植已经成为癌症免疫治疗的有前途的治疗方案。临床试验中，患有B细胞恶性肿瘤的患者接受靶向CD19的CAR-T细胞治疗已经显示了强大的抗肿瘤活性，从而给实体肿瘤利用这种治疗方法带来乐观的前景。因为CAR-T细胞能够识别区别于肿瘤细胞HLA的分子的表达，通过下调HLA和/或使得抗原传递过程中的分子变异而达到免疫逃逸传统的T 细胞攻击的效果。T细胞的这种引进或者消除额外基因的能力，使得其提供给细胞产品新的属性，在肿瘤微环境中克服免疫抑制。这篇综述将会讨论发展中的最近的概念，合成的CARs的安全性和有效性。