Antagonistic antibodies targeting co-inhibitory 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 due to insufficient induction of adaptive immune responses. Here we describe a novel vaccination method consisting of a primary dendritic cell 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. 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 dendritic cell vaccinations and induce robust T cell immune responses while providing maximum flexibility regarding the choice of antigen.
- Received August 6, 2016.
- Revision received December 20, 2016.
- Accepted January 14, 2017.
- Copyright ©2017, American Association for Cancer Research.