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

Maria Rathmann Sørensen, Peter J. Hoist, Maria A. Steffensen, Jan P. Christensen, Allan R. Thomsen

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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. (C) 2010 Elsevier Ltd. All rights reserved.
Original languageEnglish
JournalVaccine
Volume28
Issue number41
Pages (from-to)6757-6764
Number of pages8
ISSN0264-410X
DOIs
Publication statusPublished - 2010
Externally publishedYes

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