期刊
VACCINE
卷 28, 期 41, 页码 6757-6764出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2010.07.066
关键词
Cancer; Vaccination; CD8 T cells
资金
- Danish Medical Research Council
- Danish Cancer Society
- Danish Cancer Research Foundation
- Erichsen Family's Foundation
- Agnes and Poul Friis' Foundation
- Martha Margrethe and Christian Hermansens Foundation
- Foundation for Advancement of Medical Science
- Faculty of Health Sciences, Copenhagen University
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.
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