《生命科学》 2023, 35(3): 267-276

细菌与免疫疗法联用的抗肿瘤策略

陈雯霏^1,2 , 何春婷² , 张志荣² , 孙　逊^2,*

¹四川大学华西医院药剂科，代谢疾病与药物治疗研究所，成都 610041 ²四川大学华西药学院，靶向药物及释药系统教育部重点实验室，成都 610064

摘　要：

利用细菌作为一种癌症治疗手段已有较长的历史。随着对肿瘤微环境和免疫机制等相关问题的不断探究，细菌疗法已逐渐发展成为一种平台技术，为肿瘤的免疫治疗开辟了新策略、新潜能。某些细菌依靠其自身特性，能够特异性靶向肿瘤组织，不仅对肿瘤生长产生直接抑制作用，还能刺激机体产生固有和适应性免疫应答，从而显著提升抗肿瘤治疗的疗效，甚至有助于解决转移性肿瘤等难题。通过基因工程技术，从基因水平上调控细菌的分子机制来定制其生物功能，高效递送各种免疫治疗剂至肿瘤病灶处而发挥作用，达到精确调控、有效激活的目的，这是其他药物传递系统所无法比拟的。此外，肿瘤靶向型细菌介导的治疗方案既可作为单一疗法应用，也可与其他治疗方式如化疗、放疗和光热治疗等联合，以获得更佳的临床治疗结果。因此，该文主要讨论了活细菌发挥肿瘤靶向性和抗肿瘤免疫作用的关键，总结了生物工程菌用于免疫治疗的相关研究及其与其他治疗方式联合应用的优势，为细菌疗法的进一步研究与发展提供依据。

通讯作者：孙　逊 , Email:sunxun@scu.edu.cn

Synergistic strategy of bacteria and immunotherapy against tumors

CHEN Wen-Fei^1,2 , HE Chun-Ting² , ZHANG Zhi-Rong² , SUN Xun^2,*

¹Department of Pharmacy, Institute of Metabolic Diseases and Pharmacotherapy, West China Hospital, Sichuan University, Chengdu 610041, China ²Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu 610064, China

Abstract:

Using bacteria as a treatment for cancers has a long history. With the continuous exploration of the tumor microenvironment and immune system, bacterial therapy develops into a platform technology, which opens up new strategies and potentials for medical immunotherapy. Depending on their own characteristics, certain bacteria specifically target tumor tissues, directly inhibit tumor growth, and also stimulate both innate and adaptive immune responses, thus significantly improving the antitumor efficacy and even helping to solve severe problems such as metastatic tumors. Through genetic engineering technology, the molecular mechanism of bacteria can be regulated at the gene level to customize their biological function, and various therapeutic immuno-agents can be efficiently delivered into the tumor lesions, so as to achieve the purpose of precise regulation and effective activation, of which is unmatched by other drug delivery systems. In addition, the tumor-targeted bacteria-mediated treatment can be used either as monotherapy or in combination with other treatment modalities such as chemotherapy, radiotherapy, and photothermal therapy to gain more promising clinical results. This review mainly discusses the key to the tumor-targeting and antitumor immune effects of live bacteria, summarizes the related studies of bioengineered bacteria for immunotherapy and their advantages when cooperated with other therapeutic modalities, thereby providing a basis for the further research and development of bacterial therapy.

Communication Author：SUN Xun , Email:sunxun@scu.edu.cn