嵌合抗原受体修饰T细胞在恶性肿瘤中的研究进展

The progression of chimeric antigen receptor modified T cells in malignant tumor

近年来在肿瘤免疫治疗领域，嵌合抗原受体（CAR）修饰T细胞在基础研究和临床试验中取得了巨大进展。CAR由特异性单克隆抗体的可变区和CD3ζ结构域组成。CAR修饰T细胞的胞外区直接识别肿瘤相关抗原（TAA）。T细胞和靶抗原结合后可直接介导细胞毒性，并释放一些细胞因子如穿孔素、颗粒酶、干扰素-γ（IFN-γ）和肿瘤坏死因子-α（TNF-α），最终导致肿瘤细胞的坏死。尽管CAR-T细胞具有显著的抗肿瘤效应，一些基础研究和临床实验中观察到的安全性问题值得关注。

Recentyearshavewitnessedmuchprogressinbothbasicresearchandclinicaltrialsregar-ding cancer immunotherapy with chimeric antigen receptor （CAR）-engineered T cells.CAR combine the varia-ble regions of a specific monoclonal antibody （scFv）with the CD3ζendodomain.The extracellular domain of CAR-engineered T cells directly dock to the tumor-associated antigen （TAA）.When T cells bind to target anti-gens,they mediated redirected cytotoxicity and secrete a series of cytokines such as Perforin,Granzyme,Inter-feron-γ（IFN-γ）and Tumor necrosis factor-α（TNF-α）,which would eventually lead to the necrosis of tumor cells.Although the antitumor response of the CAR-engineered T cells is considered as successful and surpri-sing,it should be noted that some safety issues have been observed in other several basic researches and clinical trials.This overview focuses upon the utility and safety of the CAR-engineered T cells.