溶瘤病毒疗法的临床研究进展  

Advances in the clinical development of oncolytic viruses

作　　者：于敏 徐婕 朱淼 王菲 刘琼妮 杨丽 周天[2] 闫韶花 YU Min;XU Jie;ZHU Miao;WANG Fei;LIU Qiongni;YANG Li;ZHOU Tian;YAN Shaohua(The Second Clinical Medical College,Beijing University of Chinese Medicine,Beijing 100029,China;Department of Oncology,Dongfang Hospital,Beijing University of Chinese Medicine,Beijing 100078,China)

机构地区：[1]北京中医药大学第二临床医学院,北京100029 [2]北京中医药大学东方医院肿瘤科,北京100078

出　　处：《肿瘤》2024年第10期1033-1043,共11页Tumor

基　　金：北京中医药大学基本科研业务费(2023-JYB-JBZD-006)

摘　　要：溶瘤病毒是一种独特的抗肿瘤免疫疗法,它可以特异性地感染和裂解肿瘤细胞,并诱导激活机体自身的抗肿瘤免疫反应以攻击肿瘤。迄今为止已有3种溶瘤病毒获批上市,2005年中国首次批准重组人Ⅴ型腺病毒(H101/Oncorine)联合化疗用于治疗晚期鼻咽癌患者;2015年美国食品药品监督管理局(Food and Drug Administration,FDA)批准Ⅰ型单纯疱疹病毒(T-VEC)用于治疗初次手术后复发性黑素瘤,随后TVEC也在欧洲获批使用;2021年日本批准了第3代重组Ⅰ型单纯疱疹病毒(Delytact/G47Δ)用于治疗恶性胶质瘤。虽然中国批准H101上市在溶瘤病毒发展历程中具有突破性的意义,但是相较于T-VEC和Delytact来说,H101对于晚期鼻咽癌患者的治疗并未带来很大影响。这可能是由于其作为单药治疗无法提供完全的肿瘤治疗应答,而且中国大部分鼻咽癌患者采用放射治疗,难以从化疗联合H101中获益,因此该治疗方案还有待完善。近年来随着基因工程技术的成熟,溶瘤病毒也在不断改进完善,本综述将总结其临床研究进展,并探讨溶瘤病毒的特点及发展前景。Oncolytic virus is a unique anti-tumor immunotherapy that can specifically infect and lyse tumor cells,while inducing and activating the body's own anti-tumor immune response to attack tumors.So far,three oncolytic viruses have been approved for marketing.In 2005,China first approved recombinant human adenovirus type 5(H101/Oncorine)combined with chemotherapy for the treatment of advanced nasopharyngeal cancer patients.In 2015,the US Food and Drug Administration(FDA)approved herpes simplex virus type I(T-VEC)for the treatment of recurrent melanoma after primary surgery,T-VEC was subsequently approved in Europe.In 2021,Japan's Ministry of Health,Labour and Welfare approved thirdgeneration recombinant herpes simplex virus type I(Delytact/G47Δ)for the treatment of malignant glioma.Although the approval of H101 in China marks a breakthrough in the development of oncolytic viruses,compared to T-VEC and Delytact,H101 has not significantly impacted the treatment of patients with advanced nasopharyngeal carcinoma.This may be due to its inability to provide a complete tumor response as a monotherapy,and the fact that most nasopharyngeal carcinoma patients in China undergo radiotherapy,making it difficult for them to benefit from chemotherapy combined with H101.Therefore,this treatment regimen still needs improvement.In recent years,with the maturity of genetic engineering technology,oncolytic viruses have been continuously improved and refined.This review summarizes the clinical research progress of oncolytic viruses and discusses their characteristics and development prospects.

关 键 词：溶瘤病毒 免疫疗法 临床试验 

分 类 号：R730.51[医药卫生—肿瘤]