Human papillomavirus type 16 based L1, L2, E6, and E7 peptide microspheres induce encapsulated peptide mixture specific cytotoxic T lymphocytes and tumor regression in a murine model of cervical cancer

Background and objectives

Infection with HPV16, a high-risk human papillomavirus (HPV), can cause cervical cancer in humans. These infections carry a high risk of morbidity and mortality globally in females. This study aimed to conduct an in vivo comparison of Poly (D,L-lactic-co-glycolide) (PLGA)-encapsulated peptide mixture nanoparticles and PLGA microspheres as delivery systems for vaccines.

Methods

PLGA polymers were used to form microspheres for a therapeutic vaccine against cervical cancer. The target antigens were the L1 and L2 capsid proteins and the E6 and E7 oncoproteins from HPV16. These antigens were selected based on their immunogenicity, allergenicity, and toxicity. We predicted epitopes for cytotoxic T lymphocytes (CTLs) and helper T lymphocytes. In our investigation of CTL epitopes, we employed synthetic chimeric PLGA microsphere peptides, consisting of multiple H-2Db-restricted HPV16 peptides, coupled with other immune-potentiating adjuvants as predicted by our work.

Results

H-2Db-restricted HPV16 peptides, when administered subcutaneously, enabled CTLs to eliminate in vitro TC-1 tumor cells expressing E6 and E7 of HPV16. Additionally, TC-1 cells protected C57BL/6 mice against in vivo challenges. To address this problem, peptide-based vaccines, which are among the most effective vaccine systems, have been extensively studied. Combining peptide-based vaccinations with microsphere peptide mixture particles and delivery technologies enhances their efficacy in stimulating cellular immune responses and eliminating tumor cells.

Conclusions

This approach may provide a potential therapeutic candidate vaccine based on microsphere-encapsulated peptides for the prevention of cervical cancer caused by HPV.

Full text

https://www.xiahepublishing.com/2835-3315/CSP-2024-00003

The study was recently published in the Cancer Screening and Prevention.

Cancer Screening and Prevention (CSP) publishes high-quality research and review articles related to cancer screening and prevention. It aims to provide a platform for studies that develop innovative and creative strategies and precise models for screening, early detection, and prevention of various cancers. Studies on the integration of precision cancer prevention multiomics where cancer screening, early detection and prevention regimens can precisely reflect the risk of cancer from dissected genomic and environmental parameters are particularly welcome.

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