The combined immunization of cervical cancer therapeutic vaccine based on Listeria balanced lethal system has a significant therapeutic effect on tumor model mice
Cervical cancer is the fourth most common cancer and the fourth leading cause of cancer death in women. Effective treatment of cervical cancer is urgently needed. Tumor therapeutic vaccine is a research hotspot in tumor immunotherapy, and the tumor therapeutic vaccine based on attenuated live bacteria carrier has clinical application prospect because of its clear action site and high safety. The bacterial balanced lethal system uses nutritional screening instead of antibiotic screening to avoid the risk of the spread of antibiotic resistance. So it is generally recognized as a green carrier. In our early research, we have constructed two cervical cancer therapeutic vaccine candidates (LM-HPVCW-1 and LI-HPVCW-1) based on Listeria balanced lethal system via transforming the nutrient-deficient strains with nutrition gene complementary plasmid. The complementary plasmid contained the nutrition complementary gene, LM dal gene, and its Amp gene was replaced with asd gene to delete the antibiotic resistance. Besides, it carried the shuffled HPV-16 E6E7 fusion protein gene. In vitro experiments showed that the plasmid carried by the candidate strain could be stably passaged and the target protein could be successfully expressed. In this study, we proved that the two candidate strains were safe in vivo and induced cellular immune response. At the same time, by establishing a tumor-bearing mouse model, it was proved that the two vaccine strains combined immunization could effectively inhibit mouse tumors. The mechanism of tumor suppression may be related to breaking the immunosuppression of tumor microenvironment and inducing CD8