Introduction

The conventional prophylactic vaccines for human papillomavirus (HPV) efficiently prevent infection with high-risk HPV types, but they do not promote therapeutic effects against cervical cancer. Previously, we developed HPV16 E7-expressing Lactobacillus casei (L. casei-E7) as a therapeutic vaccine candidate for cervical cancer, which induces antitumor therapeutic effects in a TC-1 murine cancer model. To improve the therapeutic effect of L. casei-E7, we performed co-treatment with poly-gamma-glutamic acid (γ-PGA), a safe and edible biomaterial naturally secreted by Bacillus subtilis. We investigated their synergistic effect to improve antitumor efficacy in a murine cancer model. The treatment with γ-PGA did not show in vitro cytotoxicity against TC-1 tumor cells; however, an enhanced innate immune response including activation of dendritic cells was observed. Mice co-administered with γ-PGA and L. casei-E7 showed significantly suppressed growth of TC-1 tumor cells and an increased survival rate in TC-1 mouse models compared to those of mice vaccinated with L. casei-E7 alone. The administration of γ-PGA markedly enhanced the activation of natural killer (NK) cells but did not increase the E7-specific cytolytic activity of CD8⁺ T lymphocytes in mice vaccinated with L. casei-E7. Overall, our results suggest that oral administration of γ-PGA induces a synergistic antitumor effect in combination with L. casei-E7.

Methods

We did experiments as above figures.

Results

Fig. 1. The effect of γ-PGA on the viability of tumor cells and the activation of immune cells in vitro.

Fig. 2. The antitumor efficacy of oral administration with L. casei-E7 and γ-PGA.

Fig. 3. Antigen-specific CTL responses to oral administration of L. casei-E7 and γ-PGA.

Fig. 4. The increases in NK cells and CD107a-expressing NK cells in response to oral administration of L. casei-E7 and γ-PGA.

Conclusions

Taken together, γ-PGA may be a potential adjuvant for a L. casei-E7 therapeutic vaccine to improve the antitumor effect in TC-1 tumor mouse model.