Therapeutic HPV16 E7 vaccination with CD137 agonism induces tumor regression and durable immunity in mice

Prophylactic human papillomavirus (HPV) vaccines prevent new infections but do not treat established HPV-associated lesions, highlighting the need for therapeutic strategies targeting viral tumor antigens. We developed a recombinant overlapping peptide-based HPV16 E7 vaccine (ROP-E7) and evaluated its immunogenicity and antitumor activity, alone or combined with CD137 (4-1BB) agonism, in C57BL/6 mice. In tumor-free mice, ROP-E7 induced greater helper and cytotoxic T cell responses than wild-type E7. In tumor-bearing mice, ROP-E7 reduced tumor burden and improved survival, while combination treatment induced complete tumor regression and tumor-free survival beyond 100 days. These effects were associated with increased intratumoral cytotoxic T cells and reduced regulatory and exhausted T cell populations. These findings provide preclinical support for combining therapeutic HPV16 E7 vaccination with T cell co-stimulation in HPV-associated cancers.