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

Vaccine. 2010 Sep 24;28(41):6757-64. doi: 10.1016/j.vaccine.2010.07.066. Epub 2010 Aug 2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / immunology*
  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Antigens, CD / drug effects*
  • Antigens, CD / immunology
  • Antigens, Differentiation, B-Lymphocyte / immunology
  • CD40 Antigens / antagonists & inhibitors
  • CD40 Antigens / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • CTLA-4 Antigen
  • Cancer Vaccines / immunology*
  • Female
  • Histocompatibility Antigens Class II / immunology
  • Immunization, Secondary
  • Lymphocyte Depletion
  • Melanoma, Experimental / therapy*
  • Mice
  • Mice, Inbred C57BL
  • Spleen / cytology
  • Spleen / immunology


  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Differentiation, B-Lymphocyte
  • CD40 Antigens
  • CTLA-4 Antigen
  • Cancer Vaccines
  • Ctla4 protein, mouse
  • Histocompatibility Antigens Class II
  • invariant chain