Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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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

  • Kim, Eunjin (Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Yang, Jihyun (Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Sung, Moon-Hee (Department of Bio and Fermentation Convergence Technology, Kookmin University) ;
  • Poo, Haryoung (Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology)
  • Received : 2019.06.11
  • Accepted : 2019.08.01
  • Published : 2019.09.28
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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 (${\gamma}-PGA$), 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 ${\gamma}-PGA$ 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 ${\gamma}-PGA$ 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 ${\gamma}-PGA$ 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 ${\gamma}-PGA$ induces a synergistic antitumor effect in combination with L. casei-E7.

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