PD-(L)1/TGF-β双特异性抗体的临床研究进展

Clinical research progress of PD-(L)1/TGF-βbispecific antibodies

肿瘤免疫疗法是肿瘤治疗发展史的一项重大突破,程序性死亡受体1/程序性死亡配体1(PD-1/PD-L1)和嵌合抗原受体T细胞(CAR-T)等免疫疗法取得了令人欣喜的临床疗效,但由于肿瘤免疫微环境的复杂性和特殊性,单一靶点的治疗模式难以达到持久的应答,复发转移和耐药仍是大多数晚期癌症患者难以克服的问题。近年来,PD-(L)1/转化生长因子-β(TGF-β)双特异性抗体成为肿瘤免疫调节药物研发的一大热点,其包含2个功能结构域,能够同时与PD-(L)1和TGF-β结合,使T细胞恢复活性,增强免疫应答。本文主要分析近年发展较快的PD-(L)1/TGF-β双功能抗体的临床研究进展,并分析目前存在的问题,对双靶点肿瘤免疫治疗的前景做出展望,以期为双功能甚至多功能药物的研发和临床应用提供依据和参考。

Tumor immunotherapy is a major breakthrough in the history of tumor therapy.New immunooncological drugs targeting PD-1/PD-L1 and CAR-T cells have achieved gratifying clinical efficacy.However,due to the complexity and particularity of tumor immune microenvironment,it is difficult for a single target treatment mode to achieve a lasting response.Recurrence,metastasis and resistance are still difficult for most advanced cancer patients to overcome.Recently,PD-(L)1/TGF-βbispecific antibodies have become a hot spot in the research of tumor immunomodulatory drugs,which contains two functional domains and interacts with PD-(L)1 and TGF-βsimultaneously to restore the activity of T cells and enhance the immune response.This paper mainly analyzes the clinical research progress of PD-(L)1/TGF-βbifunctional antibodies,which have been developing rapidly in recent years.We further analyze the existing problems and make an outlook on the prospect of dual-target tumor immunotherapy,in order to provide basis and reference for bifunctional or multifunctional drugs.