免疫治疗相关单克隆抗体靶点在三阴性乳腺癌中的研究现状

Current status of immunotherapy-related monoclonal antibody targets in triple-negative breast cancer

乳腺癌是女性常见肿瘤之一,其中ER、PR、HER-2均为阴性的乳腺癌为三阴性乳腺癌,肿瘤免疫疗法是三阴性乳腺癌的治疗手段之一。FDA已经批准靶向于PD-L1的单克隆抗体Atezolizumab(Tecentriq)联合Abraxane治疗三阴性乳腺癌。本文综述了目前处于不同临床阶段单克隆抗体的常用免疫治疗靶点,根据作用机制的不同,这些靶点在免疫系统中起到免疫抑制或激活作用,前者如PD-1/PD-L1、CTLA-4、LAG-3、TIM-3、CD112R及Siglec-15等;后者如GITR、OX40和4-1BB等。除Tecentriq外,靶向于这些靶点的抗体多处于临床Ⅰ期和临床Ⅱ期研究,虽然发现了靶向这些抗体具有较好的安全性和一定的治疗效果,但是这些抗体能否最终应用于临床治疗则需要更深入的研究。此外,免疫治疗相关抗体多与其他靶点单抗、小分子抑制剂或化疗药物等药物联合使用,进一步增加了三阴性乳腺癌的治疗手段。

Breast cancer is one of the common tumors in women.Triple-negative breast cancer is a type of breast cancer with negative ER,PR and HER-2.Tumor immunotherapy is one of the treatments for triple-negative breast cancer.The FDA has approved the PD-L1 monoclonal antibody Atezolizumab(Tecentriq)combined with Abraxane for the treatment of triple-negative breast cancer.This article reviews the commonly used immunotherapy targets of monoclonal antibodies currently in different clinical stages.Depending on the different mechanisms,these targets play an immunosuppressive or activating role in the immune system,such as PD-1/PD-L1,CTLA-4,LAG-3,TIM-3,CD112R,Siglec-15,GITR,OX40 and 4-1BB.Except for Tecentriq,most of the antibodies are in phase I and phase II studies.Although it has been found that patients are well tolerated and have therapeutic effect,whether these antibodies can be finally applied clinical treatment requires more in-depth research.At the same time,it can be found that in addition to single use,immunotherapy-related antibodies are often used in combination with other drugs,such as other target monoclonal antibodies,small molecule inhibitors or chemotherapy drugs,which further increases triple-negative breast cancer treatment method.