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Peer-reviewedCC BY-NC 4.0iScience

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

Abstract

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.

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BibTeX
@article{ou2026therapeutic,
  title = {{Therapeutic HPV16 E7 vaccination with CD137 agonism induces tumor regression and durable immunity in mice}},
  author = {Yuqian Ou and Wenshu Lu and Hanjun Zhao and Constantinos Demetrious and Qing Zhang and Qiujie Zheng and Yanyan Jiang and Peter Kok-Ting Wan and Eric O’Neill and Lina Zhang and Shisong Jiang},
  journal = {iScience},
  year = {2026},
  month = oct,
  doi = {10.1016/j.isci.2026.118018},
  url = {https://www.cell.com/iscience/fulltext/S2589-0042(26)03401-2},
  note = {CC BY-NC 4.0},
}
RIS
TY  - JOUR
TI  - Therapeutic HPV16 E7 vaccination with CD137 agonism induces tumor regression and durable immunity in mice
AU  - Yuqian Ou
AU  - Wenshu Lu
AU  - Hanjun Zhao
AU  - Constantinos Demetrious
AU  - Qing Zhang
AU  - Qiujie Zheng
AU  - Yanyan Jiang
AU  - Peter Kok-Ting Wan
AU  - Eric O’Neill
AU  - Lina Zhang
AU  - Shisong Jiang
PY  - 2026
DA  - 2026/10/26
JO  - iScience
DO  - 10.1016/j.isci.2026.118018
UR  - https://www.cell.com/iscience/fulltext/S2589-0042(26)03401-2
AB  - 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.
SN  - 2589-0042
ER  -