Oral Administration of Poly-Gamma-Glutamic Acid Significantly Enhances the Antitumor Effect of HPV16 E7-Expressing Lactobacillus casei in a TC-1 Mouse Model
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
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.
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.
참고문헌 (28)
- Braaten KP, "Human Papillomavirus(HPV), HPV-Related Disease, and the HPV Vaccine", Rev. Obstet. Gynecol, 1, pp.2~10 (2008)
- Steller MA, "Human papillomavirus, it's genes and cancer vaccines", Cancer Cell, 3, pp.7~8 (2003)
- Adachi K, "Oral immunization with a Lactobacillus casei vaccine expressing human papillomavirus(HPV)type 16 E7 is an effective strategy to induce mucosal cytotoxic lymphocytes against HPV16 E7", Vaccine, 28, pp.2810~2817 (2010)
- Poo H, "Oral administration of human papillomavirus type 16 E7 displayed on Lactobacillus casei induces E7-specific antitumor effects in C57", BL6 mice, 2006, pp.119, 1702~1709
- Munoz N, "Epidemiologic classification of human papillomavirus types associated with cervical cancer", N. Engl. J. Med, 348, pp.518~527 (2003)
- Lee JS, "Mucosal immunization with surface-displayed severe acute respiratory syndrome coronavirus spike protein on Lactobacillus casei induces neutralizing antibodies in mice", J. Virol, 80, pp.4079~4087 (2006)
- Ault KA, "Long-term efficacy of human papillomavirus vaccination", Gynecol. Oncol, 107, pp.S27~S30 (2007)
- Diniz MO, "Immune responses and therapeutic antitumor effects of an experimental DNA vaccine encoding human papillomavirus type 16 oncoproteins genetically fused to herpesvirus glycoprotein D", Clin. Vaccine Immunol, 17, pp.1576~1583 (2010)
- Leggatt GR, "HPV vaccines : the beginning of the end for cervical cancer", Curr. Opin. Immunol, 19, pp.232~238 (2007)
- Narayan S, "Epithelial expression of human papillomavirus type 16 E7 protein results in peripheral CD8 T-cell suppression mediated by CD4+CD25+ T cells", Eur. J. Immunol, 39, pp.481~490 (2009)
- Kim JW, "Comparison of HPV DNA vaccines employing intracellular targeting strategies", Gene Ther, 11, pp.1011~1018 (2004)
- Zhang H, "High-level exogenous glutamic acid-independent production of poly-(gamma-glutamic acid)with organic acid addition in a new isolated Bacillus subtilis C10", Bioresour. Technol, 116, pp.241~246 (2012)
- 김두진, "Combination of Poly-Gamma-Glutamate and Cyclophosphamide Enhanced Antitumor Efficacy Against Tumor Growth and Metastasis in a Murine Melanoma Model", Journal of Microbiology and Biotechnology, 23(9), pp.1339~1346 (2013), 한국미생물·생명공학회[DOI]
- Poo H, "New biological functions and applications of highmolecular-mass poly-gamma-glutamic acid", Chem. Biodivers, 7, pp.1555~1562 (2010)
- Lee TY, "Oral administration of poly-gamma-glutamate induces TLR4-and dendritic cell-dependent antitumor effect", Cancer Immunol. Immunother, 58, pp.1781~1794 (2009)
- Kim TW, "Oral administration of high molecular mass polygammaglutamate induces NK cell-mediated antitumor immunity", J. Immunol, 179, pp.775~780 (2007)
- Alter G, "CD107a as a functional marker for the identification of natural killer cell activity", J. Immunol. Methods, 294, pp.15~22 (2004)
- Kim KS, "A single-center, randomized double-blind placebocontrolled study evaluating the effects of poly-gammaglutamate on human NK cell activity after an 8-week oral administration in healthy volunteers", Evid. Based Complement. Alternat. Med, 2013, pp.635960~ (2013)
- Larsen SK, "NK cells in the tumor microenvironment", Crit. Rev. Oncog, 19, pp.91~105 (2014)
- Koo GC, "Ontogeny of Nk-1+ natural killer cells, I. Promotion of Nk-1+ cells in fetal, baby, and old mice", J. Immunol, 129, pp.867~871 (1982)
- Malmberg KJ, "Natural killer cellmediated immunosurveillance of human cancer", Semin. Immunol, 31, pp.20~29 (2017)
- Miller GM, "NK cell depletion results in accelerated tumor growth and attenuates the antitumor effect of total body irradiation", Int. J. Oncol, 23, pp.1585~1592 (2003)
- Indrova M, "NK1,1+ cells are important for the development of protective immunity against MHC I-deficient, HPV16-associated tumours", Oncol. Rep, 25, pp.281~288 (2011)
- Noorpisheh Ghadimi S, "Vaccination with live Attenuated L, major and TLR4 Agonist promotes a Th1 immune response and induces protection against L. major infection in BALB", c Mice, 2018, pp.15, 74~83
- Morefield GL, "Synthetic Toll-like receptor 4 agonist enhances vaccine efficacy in an experimental model of toxic shock syndrome", Clin. Vaccine Immunol, 14, pp.1499~1504 (2007)
- Temizoz B, "Vaccine adjuvants as potential cancer immunotherapeutics", Int. Immunol, 28, pp.329~338 (2016)
- Cluff CW, "Lipid A in Cancer Therapy", pp.111~123 (2010), Springer New York
- Lee TY, "Human papillomavirus type 16 E6-specific antitumor immunity is induced by oral administration of HPV16 E6expressing Lactobacillus casei in C57BL", 6 mice, 2010, pp.59, 1727~1737