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

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    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.
    Original languageEnglish
    JournalVaccine
    Volume28
    Issue number41
    Pages (from-to)6757-64
    Number of pages8
    ISSN0264-410X
    DOIs
    Publication statusPublished - 24 Sep 2010

    Keywords

    • Adenoviridae
    • Animals
    • Antibodies, Monoclonal
    • Antigens, CD
    • Antigens, CD40
    • Antigens, Differentiation, B-Lymphocyte
    • CD8-Positive T-Lymphocytes
    • Cancer Vaccines
    • Female
    • Histocompatibility Antigens Class II
    • Immunization, Secondary
    • Lymphocyte Depletion
    • Melanoma, Experimental
    • Mice
    • Mice, Inbred C57BL
    • Spleen

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