CTLA-4 blockade enhances the CTL responses to the p53 self-tumor antigen

p53 is an attractive target for cancer immunotherapy because it is overexpr essed in a high proportion of many different types tumors, However, it is a lso expressed in normal tissues and acts as a toleragen in vivo, Previously , detailed examination of the repertoire specific for the murine p53(261-26 9) epitope in conventional and p53-deficient mice demonstrated that because of expression of p53, the CD8(+) T cells that respond to this epitope expr ess low-affinity TCRs, It has been reported that tolerance to tumor Ags Can be broken by in vivo administration of anti-CTLA-4 mAb, With the goal of o verriding tolerance and achieving optimal activation of p53-specific CTL, t he current study has assessed the effect of anti-CTLA-4 mAb on the p53-spec ific repertoire. It was found that blockade of CTLA-4 engagement at the tim e of antigenic stimulation induced a vigorous amplification of the CTL resp onses to p53 as well as proportionate expansion of the memory T cell pool. This effect was dependent on the presence of CD4(+) T cell help and correla ted with an enhancement of helper function. However, anti-CTLA-4 treatment did not enhance the avidity of the resultant p53-specific CTL populations a nd, therefore, could not reverse this important consequence of tolerance.