CTLA-4抗体治疗非小细胞肺癌研究进展

Advances in Research on CTLA-4 Antibody in Treatment of Non-Small Cell Lung Cancer

细胞毒性T淋巴细胞相关抗原-4(Totoxic T lymphocyte associated antigen-4,CTLA-4)是由活化的效应T细胞(Effector T cells,Teffs)表达的膜糖蛋白,通过与CD28竞争结合其共有的B7配体,抑制T细胞增殖、活化和细胞因子产生。阻断CTLA-4与B7的相互作用以增强T细胞的抗肿瘤活性,例如,靶向CTLA-4的抗体Ipilimumab和Tremelimumab广泛用于治疗多种人恶性肿瘤。在综述中,特别关注CTLA-4在免疫应答中的最新发现,并讨论了其抗体针对于非小细胞肺癌单独用药或与其他抗癌疗法相结合临床研究效果。同时发现,CTLA-4阻断治疗过程中的不良反应可能是该治疗策略发展的一大挑战。

Cytotoxic T lymphocyte-associated antigen-4(CTLA-4)is a membrane glycoprotein expressed by activated effector T cells(Teffs).By competing with CD28 in interactions with B7,it generates intracellar signaling which results in the inhibition of T cell proliferation and activation.Blocking the interaction between CTLA-4 and B7,the anti-tumor activity of T cells could be increased.Antibodies targeting CTLA-4,such as ipilimumab and tremelimumab,are widely used to treat a variety of human malignancies.In this review,special attention had been paid to the latest findings of the role of CTLA-4 in immune response and clinical trials related to CTLA-4 antibody alone or in combination with other therapies in the treatment of non-small cell lung cancer had been discussed.It has also been found that the adverse effects of CTLA-4 blockade therapy may be a major challenge in the development of this therapeutic strategy.