Ad‐E6/7‐HR vaccine improves the prophylactic and therapeutic efficacy in HPV‐associated cancers

作者：Yu Zhang, Ke Qiu, Jiayuan Ai, Maosen Xu, Binhan Wang, Aqu Alu, Chunjun Ye, Xiya Huang, Yu Zhang, Yingqiong Zhou, Zhiruo Song, Jie Shi, Yishan Lu, Yuquan Wei, Jianjun Ren, Yu Zhao, Ping Cheng, Xiawei Wei · 发表于：Clinical and Translational Medicine · 年份：2025 · DOI：10.1002/ctm2.70305 · 被引用次数：5 · 研究领域：Cervical Cancer and HPV Research、Virus-based gene therapy research、Immunotherapy and Immune Responses

Abstract Background High‐risk human papillomavirus (HPV), especially HPV16, is closely correlated with certain cancers. E6 and E7 proteins of HPV16 play critical roles in oncogenesis, making them optimal targets for treating HPV‐associated cancers. Here, we engineered an innovative vaccine, Ad‐E6/7‐HR, designed to evoke immune responses through the incorporation of self‐assembling heptad‐repeat 1 (HR1) and HR2 originated from Severe acute respiratory syndrome coronavirus 2. Methods Ad‐E6/7‐HR was constructed utilising a replication‐defective human adenovirus serotype 5 vector and evaluated its immunogenicity and therapeutic efficacy in murine models. We verified the antitumour efficacy of the vaccine in TC‐1 subcutaneous and pulmonary models. Flow cytometry, enzyme‐linked immunospot assay, and immunofluorescence staining were used to assess the cellular immunogenicity of Ad‐E6/7‐HR. Results Ad‐E6/7‐HR induced robust immune responses, significantly increasing antigen‐specific CD8 + T cells. The vaccine also enhanced memory T‐cell generation and induced potent cytokine secretion, as exemplified by interferon‐γ and tumour necrosis factor‐α. Ad‐E6/7‐HR conferred complete protection against tumour growth in the prophylactic model. In therapeutic settings, Ad‐E6/7‐HR significantly reduced tumour size and improved survival. Furthermore, Ad‐E6/7‐HR reshaped the tumour microenvironment by increased CD8 + T‐cell recruitment and reduced immunosuppressive cells, like myeloid‐derived supp...