Gtl001, A Bivalent Therapeutic Vaccine Against Human Papillomavirus 16 And 18, Induces Antigen-Specific Cd8(+) T Cell Responses Leading To Tumor Regression

BackgroundProphylactic vaccines are available for women and girls not yet infected with HPV, but women already infected with HPV need a treatment to prevent progression to high-grade cervical lesions and cancer. GTL001 is a bivalent therapeutic vaccine for eradicating HPVinfected cells that contains HPV16 E7 and HPV18 E7 both fused to detoxified adenylate cyclase from Bordetella pertussis, which binds specifically to CD11b(+) antigen-presenting cells. This study examined the ability of therapeutic vaccination with GTL001 adjuvanted with topical imiquimod cream to induce functional HPV16 E7-and HPV18 E7-specific CD8 + T cell responses.MethodsBinding of GTL001 to human CD11b was assessed by a cell-based competition binding assay. Cellular immunogenicity of intradermal vaccination with GTL001 was assessed in C57BL/6 mice by enzyme-linked immunospot assay and in vivo killing assays. In vivo efficacy of GTL001 vaccination was investigated in the TC-1 murine HPV16 E7-expressing tumor model.ResultsGTL001 bound specifically to the human CD11b/CD18 receptor. GTL001 adjuvanted with topical 5% imiquimod cream induced HPV16 E7 and HPV18 E7-specific CD8(+) T cell responses. This CD8(+) T-cell response mediated in vivo killing of HPV E7-expressing cells. In the HPV16 E7-expressing tumor model, GTL001 adjuvanted with imiquimod but not imiquimod alone or a combination of unconjugated HPV16 E7 and HPV18 E7 caused complete tumor regression.ConclusionsGTL001 adjuvanted with topical 5% imiquimod is immunogenic and induces HPV16 E7 and HPV18 E7-specific CD8(+) T cell responses that can kill HPV E7-expressing cells and eliminate HPV E7-expressing tumors.