《生命科学》 2023, 35(11): 1462-1474
溶瘤病毒联合CAR-T细胞治疗实体瘤研究进展
摘 要：
嵌合抗原受体修饰的T 细胞(chimeric antigen receptor T cells, CAR-T) 疗法属于肿瘤免疫治疗的范畴。该疗法在血液系统恶性肿瘤治疗中表现优异，但在实体瘤治疗中存在诸多挑战。近年来，溶瘤病毒 (oncolytic viruses, OVs) 在针对黑色素瘤、脑胶质瘤等实体瘤适应证的临床试验中展现出良好的疗效。溶瘤病毒一方面选择性地在肿瘤细胞中复制杀伤肿瘤细胞，另一方面通过激活机体自身的免疫系统发挥抗肿瘤作用。因此，溶瘤病毒与免疫检查点抑制剂、肿瘤浸润淋巴细胞疗法(tumor infiltrating lymphocytes, TIL) 等免疫疗法的联合应用也在广泛开展。目前研究表明，溶瘤病毒不仅能够增加CAR-T 细胞的抗肿瘤活性，而且通过传递肿瘤相关抗原或特异性抗原来增强CAR-T 细胞对肿瘤的杀伤作用，同时溶瘤病毒还可以帮助CAR-T 细胞克服免疫抑制性的肿瘤微环境。两种疗法的联合应用在临床前研究中展现出了良好的疗效和安全性，能够解决CAR-T 在实体瘤治疗领域的瓶颈，具有广阔的临床转化前景。本文就溶瘤病毒与CAR-T 细胞联合治疗实体瘤的药效及相关机制研究展开论述。
通讯作者：刘滨磊 , Email:liubl@hbut.edu.cn
Abstract:
Chimeric antigen receptor modified T cells (CAR-T) therapy belongs to the field of tumor immunotherapy. CAR-T therapy has shown good efficacy in the treatment of hematological malignancies, but there are many challenges in the treatment of solid tumors. In recent years, oncolytic viruses (OVs) have demonstrated promising efficacy in clinical trials for solid tumors such as melanoma and glioma. Oncolytic viruses selectively replicate and kill tumor cells while activating the body's immune system to exert anti-tumor effects. Therefore, combining oncolytic viruses with immune checkpoint inhibitors, TIL, and other immunotherapies is widely carried out. Research indicates that oncolytic viruses can enhance the anti-tumor activity of CAR-T cells by transmitting tumor-related or specific antigens and helping CAR-T cells overcome the immune-suppressive tumor microenvironment. The combination of these two therapies has shown good efficacy and safety in preclinical studies, offering a promising solution to the bottleneck of CAR-T in treating solid tumors. In this article we discuss the efficacy and related mechanisms of oncolytic viruses and CAR-T cell combination therapy for solid tumors.
Communication Author：LIU Bin-Lei , Email:liubl@hbut.edu.cn
