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| Therapeutic Efficacy of Mouse (Mus musculus) Cervical Cancer Therapeutic Vaccine Based on the Attenuated Gene Deletion Listeria monocytogenes |
| WANG Feng-Ting*, SUN Jing*, LIU Chen, CHENG Yin, JIANG Xin, ZHU Yi-Ran, WEI Fang-Fang, ZHANG Xian, SONG Hou-Hui**, CHENG Chang-Yong** |
| College of Animal Science ＆ Technology·College of Veterinary Medicine, Zhejiang A＆F University/Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province/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, Hangzhou 311300, China |
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Abstract The attenuated bacterial pathogen Listeria monocytogenes (LM) have been widely studied for cancer immunotherapy as a safe vaccine via presenting tumor-associated antigens. The most common attenuation strategy is to delete the virulence-associated genes. The Listeria attenuated double genes deletion strain ΔactAΔinlB (ΔAB) has become the ideal platform for cancer vaccine research and development. This study aim to develop a ΔAB-based vaccine candidate that can efficiently express and present the cervical cancer-associated E7 antigen (ΔAB-E7) to evaluate the immunotherapeutic efficacy in the mice (Mus musculus) cervical cancer model. The bacterial genetic methods were employed to construct the ΔAB and ΔAB-E7 by introducing E7 with in-frame fusion to the virulence factor listeriolysin O (LLO). The ΔAB-E7 was verified whether the E7 antigen could be expressed in fusion with LLO by Western blot. The infection characteristics of these strains were studied, including in vitro and intracellular growth, bacterial proliferation, and pathogenicity in mice. Then, the immunotherapy efficacy of ΔAB-E7 was evaluated on the mice cervical cancer model by tracking tumor growth. The results showed that ΔAB-E7 could efficiently express and secrete LLO-fused E7, the in vitro and intracellular growth abilities of ΔAB and ΔAB-E7 were comparable to those of wild-type strain, while the virulence was significantly attenuated in mice with the highly-reduced proliferation ability in mice organs. Importantly, vaccination of ΔAB-E7 could inhibit cervical cancer growth in mice, eliciting promising anti-tumor efficacy. Collectively, this study present a favorable Listeria-based vaccine candidate against cervical cancer, which provides new strategies for future research and applications of immunotherapies for human cervical cancer and other cancers.
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Received: 06 December 2021
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| Fund:* These authors contributed equally to this work |
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Corresponding Authors:
** lamge@zafu.edu.cn; songhh@zafu.edu.cn
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