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Oral Administration of Poly-Gamma-Glutamic Acid Significantly Enhances the Antitumor Effect of HPV16 E7-Expressing Lactobacillus casei in a TC-1 Mouse Model

Journal of Microbiology and Biotechnology 2019년 29권 9호 p.1444 ~ 1452
 ( Kim Eun-Jin ) - Korea Research Institute of Bioscience and Biotechnology Infectious Disease Research Center

 ( Yang Ji-Hyun ) - Korea Research Institute of Bioscience and Biotechnology Infectious Disease Research Center
 ( Sung Moon-Hee ) - Kookmin University Department of Bio and Fermentation Convergence Technology
 ( Poo Ha-Ryoung ) - Korea Research Institute of Bioscience and Biotechnology Infectious Disease Research Center

Abstract


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.

키워드

Poly-gamma-glutamic acid; adjuvant; Lactobacillus casei; HPV16 E7; cervical cancer; natural killer cells
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