ArticleProceedings of the National Academy of Sciences of the United States of America2015
Unique potential of 4-1BB agonist antibody to promote durable regression of HPV+ tumors when combined with an E6/E7 peptide vaccine.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 97 citations in OpenAlex.
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- The Role of Monoclonal Antibodies as Therapeutics in HPV-Related Head and Neck Cancers: An Updated Review.Antibodies (Basel, Switzerland) · 2025Review
- FLASH radiotherapy spares lymphocytes in tumor-draining lymph nodes and increases infiltration of immune cells in tumors.bioRxiv : the preprint server for biology · 2025Article
- Development and evaluation of a novel E7 multi-epitopic vaccine for human papillomavirus type 16: design, expression, purification, and immunological characterization.BMC infectious diseases · 2025Article
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- The multifaceted role of PCSK9 in cancer pathogenesis, tumor immunity, and immunotherapy.Medical oncology (Northwood, London, England) · 2024Review
- Preclinical evaluation of two phylogenetically distant arenavirus vectors for the development of novel immunotherapeutic combination strategies for cancer treatment.Journal for immunotherapy of cancer · 2024Article
- Oncolytic Adenovirus Armed with a Novel Agonist of the CD137 Immune Checkpoint Stimulator Suppresses Tumor Growth.Vaccines · 2024Article
- Genetic fusion of CCL11 to antigens enhances antigenicity in nucleic acid vaccines and eradicates tumor mass through optimizing T-cell response.Molecular cancer · 2024Article
- Immunity from NK Cell Subsets Is Important for Vaccine-Mediated Protection in HPV+ Cancers.Vaccines · 2024Article
- Peritumoral administration of immunomodulatory antibodies as a triple combination suppresses skin tumor growth without systemic toxicity.Journal for immunotherapy of cancer · 2024Article
- Cancer vaccines in the clinic.Bioengineering & translational medicine · 2024Review
- HPV-associated head and neck cancer is characterized by distinct profiles of CD8Cancer immunology, immunotherapy : CII · 2023Article
- A Therapeutic DNA Vaccine Targeting HPV16 E7 in Combination with Anti-PD-1/PD-L1 Enhanced Tumor Regression and Cytotoxic Immune Responses.International journal of molecular sciences · 2023Article
- Proinflammatory allogeneic dendritic cells enhance the therapeutic efficacy of systemic anti-4-1BB treatment.Frontiers in immunology · 2023Article
- Targeting CD137 (4-1BB) towards improved safety and efficacy for cancer immunotherapy.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Antibody modulation of T-cell coinhibitory (e.g., CTLA-4) or costimulatory (e.g., 4-1BB) receptors promotes clinical responses to a variety of cancers. Therapeutic cancer vaccination, in contrast, has produced limited clinical benefit and no curative therapies. The E6 and E7 oncoproteins of human papilloma virus (HPV) drive the majority of genital cancers, and many oropharyngeal tumors. We discovered 15-19 amino acid peptides from HPV-16 E6/E7 for which induction of T-cell immunity correlates with disease-free survival in patients treated for high-grade cervical neoplasia. We report here that intranasal vaccination with these peptides and the adjuvant alpha-galactosylceramide elicits systemic and mucosal T-cell responses leading to reduced HPV(+) TC-1 tumor growth and prolonged survival in mice. We hypothesized that the inability of these T cells to fully reject established tumors resulted from suppression in the tumor microenvironment which could be ameliorated through checkpoint modulation. Combining this E6/E7 peptide vaccine with checkpoint blockade produced only modest benefit; however, coadministration with a 4-1BB agonist antibody promoted durable regression of established genital TC-1 tumors. Relative to other therapies tested, this combination of vaccine and α4-1BB promoted the highest CD8(+) versus regulatory FoxP3(+) T-cell ratios, elicited 2- to 5-fold higher infiltration by E7-specific CTL, and evoked higher densities of highly cytotoxic TcEO (T cytotoxic Eomesodermin) CD8 (>70-fold) and ThEO (T helper Eomesodermin) CD4 (>17-fold) T cells. These findings have immediate clinical relevance both in terms of the direct clinical utility of the vaccine studied and in illustrating the potential of 4-1BB antibody to convert therapeutic E6/E7 vaccines already in clinical trials into curative therapies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.