Enhanced Effect of Mycobacterium tuberculosis-Related Antigens in Cervical Cancer Immunotherapy Based on Attenuated Listeria monocytogenes
LIU Chen1, SONG Ya-Wen1, JIANG Xin1, SUN Jing1, JIANG Ling-Li2, SONG Hou-Hui1,*, CHENG Chang-Yong1,*
1 College of Animal Science and Technology/College of Veterinary Medicine/Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province/Zhejiang Provincial Engineering Research Center for Animal Health Diagnostics/Advanced Technology, Zhejiang International Science and Technology Cooperation Base for Veterinary Medicine and Health Management/China-Australia Joint Laboratory for Animal Health Big Data Analytics, Zhejiang A&F University, Hangzhou 311300, China; 2 NingBo College of Health Sciences, Ningbo 315100, China
Abstract：Listeria monocytogenes has been increasingly studied as a delivery vector in various cancer and infectious disease immunotherapies, as it can induce robust immune responses in the host. In this study, the tumor vaccine strains, LM-Ag85B and LM-ESAT6 were constructed by fusing the Mycobacterium tuberculosis antigens Ag85B (Antigen 85B) and ESAT6 (6 kD early secreted antigen target) with the virulence factor listeriolysin O (LLO), which served as the basis in the preliminary laboratory experiments. The Western blot was employed to confirm the fusion expression and normal secretion of antigens with LLO. The in vitro growth capability and hemolytic activity of LM-Ag85B and LM-ESAT6 were investigated using bacterial infection biology methods. The therapeutic effects of combined application of LM-Ag85B and LM-ESAT6 with LM-E7 (expressing cervical cancer-related antigen E7) were evaluated in a mouse model of cervical cancer. The results revealed that LM-Ag85B and LM-ESAT6 were able to express and secrete the carried Ag85B and ESAT6 antigens, respectively. The in vitro growth capability of LM-Ag85B and LM-ESAT6 showed no significant difference compared to the wild-type strain, while their hemolytic activity was lower than that of the wild-type strain. In the mouse model of cervical cancer treatment, the experimental groups receiving combined application of LM-Ag85B, LM-ESAT6, and LM-E7 exhibited significant inhibition of tumor growth compared to the control group, indicating favorable therapeutic effects. This study demonstrates that the Mycobacterium tuberculosis antigens can provide enhanced tumor therapeutic efficacy for the LM-E7 based cervical cancer, which significantly promotes future applications of bacterial-based tumor immunotherapy..
刘晨, 宋亚雯, 蒋昕, 孙静, 江玲丽, 宋厚辉, 程昌勇. 结核分枝杆菌相关抗原在基于减毒单增李斯特菌为载体的宫颈癌免疫治疗中的增强效果[J]. 农业生物技术学报, 2023, 31(11): 2367-2376.
LIU Chen, SONG Ya-Wen, JIANG Xin, SUN Jing, JIANG Ling-Li, SONG Hou-Hui, CHENG Chang-Yong. Enhanced Effect of Mycobacterium tuberculosis-Related Antigens in Cervical Cancer Immunotherapy Based on Attenuated Listeria monocytogenes. 农业生物技术学报, 2023, 31(11): 2367-2376.
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