Recombinant lactococcus lactis expressing HPV-16 E6E7 dual antigens for potential cervical cancer treatment enhances dendritic cell vaccines efficacy

表达HPV-16 E6E7双抗原的重组乳酸乳球菌可增强树突状细胞疫苗的疗效,有望用于宫颈癌治疗。

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Abstract

AIMS: Anti-tumor vaccines that target the early proteins E6 and E7 of human papillomavirus (HPV) type 16 represent a potential immunotherapy for cervical cancer, although underlying mechanisms remain unclear. Lactococcus lactis (L.L) is generally regarded as safe (GRAS) which has potential as vehicle. Study investigated the immunoregulatory effect of L.L on dendritic cells (DCs) activation. Besides, antigen delivery and anti-tumor effects of DC-based vaccine prepared with recombinant L.L vaccine (L.L-De) carrying prokaryotic-eukaryotic HPV-16 E6E7 fusion antigen were explored. METHODS: Study performed flow cytometry and MTT to analyze the adjuvant efficacy in promoting DC activation and proliferative capacity of T lymphocytes. The anti-tumor effect of DC vaccine prepared with L.L-De was assessed in C57BL6 tumor model. RESULTS: Recombinant L.L carrying the expression frame for HPV-16 E6E7 fusion protein in prokaryotic-eukaryotic expression systems exhibited antigen-promoting and cross-presenting adjuvant activity successfully. the developed DC-L.L-De vaccine induced antigen-specific Th-1 and cytotoxic T lymphocyte responses, which inhibited TC-1 tumor growth. CONCLUSIONS: This study demonstrated that recombinant L.L which carries a dual-expression antigen frame, is a promising vector for tumor antigen delivery.

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