基于重组减毒沙门氏菌载体递送疫苗及药物的肿瘤免疫治疗研究新进展

Advances in vaccine and drug delivery for tumor immunotherapy based on recombinant attenuated Salmonella vector

沙门氏菌介导的肿瘤免疫治疗方法已经成为抗肿瘤研究领域的热点之一。首先,沙门氏菌作为兼性厌氧菌,能够特异性地定植在肿瘤区域,直接杀伤肿瘤细胞或诱导机体产生免疫反应,介导包括巨噬细胞、中性粒细胞和T细胞等在内的免疫细胞浸润从而发挥抗肿瘤效应。其次,沙门氏菌具有高度遗传修饰性,可被改造为毒力减低或精准靶向的重组沙门氏菌。此外,重组沙门氏菌还可作为疫苗、细胞毒性药物、RNAi和纳米颗粒递送的有效平台,在治疗的同时还可预防肿瘤的复发和转移。如重组沙门氏菌载体活疫苗裂解系统,能够加强肿瘤抗原呈递,促进T细胞发挥杀伤效应。本文介绍了减毒沙门氏菌载体的抗肿瘤免疫特性和肿瘤靶向性,并对以重组减毒沙门氏菌为递送系统进行肿瘤免疫治疗的研究进展进行综述。

Salmonella-mediated immunotherapeutic approaches for tumors have become one of hot spots in the field of antitumor research.First,Salmonella,as a parthenogenic anaerobic bacterium,is able to specifically colonize the tumor area.It can also directly kill tumor cells and induce immune responses in body,mediating the infiltration of immune cells such as macrophages,neutrophils and T cells to exert anti-tumor effects.Second,based on the highly genetically modified features,it can be modified to become virulence-reduced or precisely targeted recombinant Salmonella.In addition,recombinant Salmonella could serve as an efficient platform for the delivery of cancer vaccine,cytotoxic agents,RNAi and nanoparticles,which showed a strong inhibitory effect on growth of cancer,and exhibited a prevention of tumor recurrence and metastasis.For example,a vaccine lysis system based on recombinant attenuated Salmonella vector,which can enhance tumor antigen presentation and promote antitumor effects of T-cell.This review describes the antitumor immune properties and tumor targeting of Salmonella,and also elaborate the progress of research on tumor immunotherapy using recombinant attenuated Salmonella as a delivery system.