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

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.

• Authors: Eunjin Kim, Jihyun Yang, Moon-Hee Sung, Haryoung Poo
• Journal: Journal of microbiology and biotechnology (J Microbiol Biotechnol) Vol. 29 Issue 9 Pg. 1444-1452 (Sep 28 2019) ISSN: 1738-8872 [Electronic] Korea (South)
• PMID: 31387341 (Publication Type: Journal Article)

Chemical References

• Adjuvants, Immunologic
• Cancer Vaccines
• Papillomavirus E7 Proteins
• Papillomavirus Vaccines
• oncogene protein E7, Human papillomavirus type 16
• poly(gamma-glutamic acid)
• Polyglutamic Acid

Topics

• Adjuvants, Immunologic (administration & dosage, pharmacology)
• Administration, Oral
• Animals
• Cancer Vaccines (administration & dosage, genetics, immunology)
• Cell Survival
• Cells, Cultured
• Dendritic Cells (immunology)
• Female
• Immunity, Innate (drug effects)
• Killer Cells, Natural (immunology)
• Lacticaseibacillus casei (genetics)
• Lymphocyte Activation (drug effects)
• Mice
• Mice, Inbred C57BL
• Papillomavirus E7 Proteins (genetics, immunology)
• Papillomavirus Vaccines (administration & dosage, genetics, immunology)
• Polyglutamic Acid (administration & dosage, analogs & derivatives, pharmacology)
• RAW 264.7 Cells
• Uterine Cervical Neoplasms (prevention & control)
• Xenograft Model Antitumor Assays