1)昆明理工大学医学院,昆明 650500;2)云南省第一人民医院,昆明 650032
国家自然科学基金(81860281,81960555),云南省科技厅科技 计划(2019FB108),云南省中青年学术和技术带头人后备人才项 目(202105AC160030),云南省高层次卫生计生技术人才培养经费 (D-2017054), 云南省卫生内设研究机构(2017NS213, 2018NS234) 和云南省临床病毒学重点实验室开放课题 (202005AG070062-015) 资助项目。
1)Medical School, Kunming University of Science and Technology, Kunming 650500, China;2)The First People’s Hospital of Yunnan Province, Kunming 650032, China
This work was supported by grants from The National Natural Science Foundation of China (81860281, 81960555), Science and Technology Plan Project of Science&Technology Department of Yunnan Province (2019FB108), Top Experts Training Project for the Academy and Technology in Kunming City and Yunnan Province (202105AC160030), Yunnan Health Training Project of High Level Talents (D-2017054), Research Project of Health Commission of Yunnan Province (2017NS213, 2018NS234), and Open Project of Yunnan Provincial Key Laboratory of Clinical Virology Science Research Foundation of Yunnan Provincial (202005AG070062-015).
溶瘤病毒疗法属于免疫治疗的手段之一。其可通过病毒特异性地感染裂解肿瘤细胞和激活肿瘤免疫两种途径来达到杀伤肿瘤的目的;同传统疗法比,具有安全、高效、副作用小等优点。流感病毒自1900年代首次发现其可能作为“有益”的病毒缓解白血病病情以来,不断有研究证明流感病毒具有杀伤肿瘤细胞的能力;利用反向遗传操作技术对病毒进行改造,有望将其发展成为一种更加安全、有效的肿瘤治疗生物制剂。本文将对近年来溶瘤流感病毒利用肿瘤分泌的胰蛋白酶促进病毒感染并在RAS基因突变导致干扰素缺陷的肿瘤中复制来提高肿瘤靶向性,编码CTLA-4的单链抗体或HER-2增强流感病毒的抗癌特异性及作为外源基因IL-2、IL-15、GM-CSF和抗PD-1单克隆抗体的载体激活机体免疫几个方向进行综述。
Oncolytic virus therapy belongs to immunotherapy. It can achieve the purpose of killing tumors by virus-specific infection and activating tumor immunity. Compared with traditional therapies, it has the advantages of safety, efficiency, and less side effects. A variety of viruses have been studied, and commonly used viruses include adenovirus, vaccinia virus, herpes virus, reovirus, parvovirus, Newcastle disease virus, Coxsackie virus, etc. for oncolytic therapy, and have been used in clinical and achieved good therapeutic effect. With the continuous development of oncolytic viruses, there are currently 4 oncolytic viruses approved for marketing: Rigvir?, Oncorine?, Imlygic? and Delytact?. Currently many viruses used in tumor treatment. Since the influenza virus were first discovered in the 1900s as a “beneficial” virus to alleviate leukemia, there have been studies that prove that influenza viruses have the ability to kill tumor cells. Researchers have made many attempts in the process of fighting influenza. The process of developing inactivated vaccines, live attenuated vaccines, and subunit recombinant influenza vaccines accumulated valuable experience for further building oncolytic viruses. Influenza viruses were one of the first viruses to be used in tumor treatment. With the development of molecular biology, it is now possible to artificially intervene in many of the traits of viruses. The mechanism of oncolytic influenza virus become more and more in-depth, and the current mode of action of oncolytic influenza virus can be summarized as the following 3 points: (1) the virus directly lyses tumor cells; (2) viruses activate immunity to kill tumor cells; (3) viruses expressing exogenous genes as vectors improves both of these abilities. In this review, the modified influenza virus has stronger selectivity for pancreatic enzymes secreted by tumor cells with interferon-deficient RAS mutations to improve tumor targeting. The single-chain antibody encoding CTLA-4 or HER-2 enhances the anticancer specificity of influenza virus and acts as the carrier of foreign genes IL-2, IL-15, GM-CSF and anti-PD-1 to activate immunity are reviewed.
梁亮,唐磊,石华冉,方中岳,欧霞,杨帆,张继虹,杨景晖.溶瘤性流感病毒的研究进展[J].生物化学与生物物理进展,2022,49(10):1910-1917
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