CD40 Signaling Drives Potent Cellular Immune Responses in Heterologous Cancer Vaccinations

Cancer Res. 2017 Apr 15;77(8):1918-1926. doi: 10.1158/0008-5472.CAN-16-2089. Epub 2017 Feb 15.


Antagonistic antibodies targeting coinhibitory receptors have revolutionized the treatment of cancer by inducing durable immune responses and clinical remissions in patients. In contrast, success of agonistic costimulatory antibodies has thus far been limited because of the insufficient induction of adaptive immune responses. Here, we describe a novel vaccination method consisting of a primary dendritic cell (DC) immunization followed by a composite vaccination, including an agonistic CD40 antibody, soluble antigen, and a TLR3 agonist, referred to as CoAT. In mice, DC/CoAT prime-boost vaccinations targeting either MHC class I or II neoantigens or tumor-associated antigens rendered up to 60% of the total T-cell population specific for a single tumor epitope. DC/CoAT induced durable and complete remissions of large subcutaneous tumors without detectable side effects. Thus, booster vaccinations with agonistic costimulatory antibodies represent an ideal means to amplify DC vaccinations and induce robust T-cell immune responses while providing maximum flexibility regarding the choice of antigen. Cancer Res; 77(8); 1918-26. ©2017 AACR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD40 Antigens / agonists
  • CD40 Antigens / immunology*
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / immunology*
  • Colorectal Neoplasms / immunology*
  • Colorectal Neoplasms / therapy*
  • Dendritic Cells / immunology*
  • Dendritic Cells / transplantation*
  • Immunotherapy, Adoptive / methods
  • Melanoma, Experimental / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Oligopeptides / immunology
  • Toll-Like Receptor 3 / agonists
  • Toll-Like Receptor 3 / immunology
  • Vaccination / methods


  • CD40 Antigens
  • Cancer Vaccines
  • Oligopeptides
  • TLR3 protein, mouse
  • Toll-Like Receptor 3