Cited by 55Immunotherapy and Immune ResponsesCancer Immunotherapy and BiomarkersT-cell and B-cell Immunology

Adenoviral vaccination combined with CD40 stimulation and CTLA-4 blockage can lead to complete tumor regression in a murine melanoma model

Sorensen, Maria R., Holst, Peter J., Steffensen, Maria A., Christensen, Jan P., Thomsen, Allan R.·2010·Vaccine

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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Crossref · 10.1016/j.vaccine.2010.07.066

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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).”

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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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