嵌合抗原受体T细胞在实体瘤治疗中的应用

Chimeric Antigen Receptor T Cells for Treatment of Solid Tumor

嵌合抗原受体（chimeric antigen receptors, CAR）修饰的T细胞不受主要组织相容性复合体（ major histocompatibility complex, MHC）分子的限制性，能有效地识别靶抗原，重定向T细胞特异性杀伤肿瘤细胞，是肿瘤治疗中很有前景的新方法。CART细胞在治疗血液学肿瘤中效果显著，但是在实体瘤治疗中有许多障碍。由于多数潜在实体瘤靶点是非特异的，在健康组织中也表达，由此产生相比血液肿瘤CART细胞治疗中B细胞缺失更不可耐受的副反应，如细胞因子释放综合征和靶向非肿瘤毒性，有时甚至是致命性的。随着CART治疗肿瘤技术的不断发展，临床前及临床试验显示了较好的有效性、安全性，CART细胞治疗仍是吸引人的治疗方法。多种潜在实体瘤靶点在考虑中，如神经节苷脂GD2、白介素13受体alpha2亚基 （Interleukin 13 receptor α2, IL13 Rα2）、间皮素等。现介绍CART细胞治疗实体瘤的不良反应，重点关注近年来报道的实体瘤潜在治疗靶点。

Chimeric antigen receptor-modified T （CART） cells are capable of recognizing tar- get antigen in a major histocompatibility complex （MHC） -independent manner, redirecting T ceils to eliminate tumor cells specifically. It is a promising method for tumor treatment. CART cells have impressive clinical efficacy in treating patient with hematological malignancies, but there are several obstacles in CAR T-cell therapy for solid tumors. Since most potential solid tumor targets are non- specific, and expressed in healthy tissues as well, the adverse effects may be less tolerable than the B cell aplasia associated with hematologic CART cell therapies, such as the cytokine-release syn- drome, ＂ on-target, off-tumor＂ toxicity, and some adverse effects are even fetal in some ca- ses. With recent advancements in CART technology, its safety and efficacy have been shown in some preclinical models and clinical trials, making it attractive therapy. A wide variety of potential solid tumor targets are under consideration, such as GD2, IL13 α2, HER2, mesothelin. Herein, in this review we describe the adverse effects of CART cell therapy in solid tumor with a particular em- phasis on the potential solid tumor targets.