Conversion of tumor-specific CD4(+) T-cell tolerance to T-cell priming through in vivo ligation of CD40

Tumor antigen-specific T-cell tolerance limits the efficacy of therapeutic cancer vaccines. Antigen-presenting cells mediate the induction of T-cell t olerance to self-antigens. We therefore assessed the fate of tumor-specific CD4(+) T cells in tumor-bearing recipients after in vivo activation of ant igen-presenting cells with antibodies against CD40. Such treatment not only preserved the responsiveness of this population, but resulted in their end ogenous activation. Established tumors regressed in vaccinated mice treated with antibody against CD40 at a time when no response was achieved with va ccination alone. These results indicate that modulation of antigen-presenti ng cells may be a useful strategy for enhancing responsiveness to immunizat ion.