Adenoviral vaccination combined with CD40 stimulation and CTLA-4 blockage can lead to complete tumor regression in a murine melanoma model
Abstract
Therapeutic vaccination with replication deficient adenovirus expressing a viral antigen linked to invariant chain was recently found to markedly delay the growth of B16.F10 melanomas expressing the same antigen; however, complete regression of the tumors was never observed. Here we show that the delay in tumor growth can be converted to complete regression and long-term survival in 30-40% of the mice by a booster vaccination plus combinational treatment with agonistic anti-CD40 monoclonal antibodies (mAb) and anti-CTLA-4 mAb. Regarding the mechanism underlying the improved clinical effect, analysis of the tumor-specific response revealed a significantly prolonged tumor-specific CD8 T cell response in spleens of the mice receiving the combinational treatment compared with mice receiving either treatment individually. Matching this, CD8 T cell depletion completely prevented tumor control. These results indicate that even with a strong tumor vaccine candidate, combinatorial treatment may be required to obtain clinically relevant results.
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In mouse melanoma models, combination of anti-CTLA-4 with GM-CSF or with agonistic antibodies targeting CD40 increased tumor rejection synergistically.
“Mouse melanoma models, for example, have shown that the combination of anti-CTLA-4 with cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) or with agonistic antibodies targeting costimulatory receptors such as CD40, increased tumor rejection in a synergistic manner (121, 122).”
From Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations (2018) · cites this paper as [122]
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Myers, J. W., Peoples, G. E., & Clifton, G. T. (2020) · Springer eBooks · doi:10.1007/978-3-030-50287-4_6
Targeting VISTA as a novel immunotherapy for skin cancer
Hou, Y., Chen, X., & Chen, C. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1815113
- Authors
- Sorensen, M. R., Holst, P. J., Steffensen, M. A., Christensen, J. P., & Thomsen, A. R.
- Affiliations
- University of Copenhagen (DK)
- Corresponding author
- Thomsen, Allan R.
- Venue
- Vaccine
- Publisher
- Elsevier BV
- Published
- 2010-09
- Volume
- 28
- Issue
- 41
- Pages
- 6757-6764
- ISSN
- 0264-410X (ISSN-L)
- OpenAlex
- W2053248202
- Cited by
- 55
- References
- 43
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 1 · 2020: 4 · 2019: 5 · 2018: 6 · 2017: 2 · 2016: 2 · 2015: 3 · 2014: 8 · 2013: 8 · 2012: 4
- FWCI
- 2.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Vaccine (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- CD40 agonism, CTLA-4 blockade, melanoma, B16F10 melanoma, tumor regression, CD8+ T cells, CD74, tumor-specific T cell responses, combination immunotherapy, booster vaccination
- MeSH terms
- Adenoviridae, Animals, Antibodies, Monoclonal, Antigens, Differentiation, B-Lymphocyte, Histocompatibility Antigens Class II, Female, Immunization, Secondary, Lymphocyte Depletion, Melanoma, Experimental, Mice, Inbred C57BL, Spleen, Antigens, CD, CD8-Positive T-Lymphocytes, CD40 Antigens, Cancer Vaccines, Mice, CTLA-4 Antigen
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