PT  - JOURNAL ARTICLE
AU  - Hernández, Javier
AU  - Ko, Alice
AU  - Sherman, Linda A.
TI  - CTLA-4 Blockade Enhances the CTL Responses to the p53 Self-Tumor Antigen
AID  - 10.4049/jimmunol.166.6.3908
DP  - 2001 Mar 15
TA  - The Journal of Immunology
PG  - 3908--3914
VI  - 166
IP  - 6
4099  - http://www.jimmunol.org/content/166/6/3908.short
4100  - http://www.jimmunol.org/content/166/6/3908.full
SO  - J. Immunol.2001 Mar 15; 166
AB  - p53 is an attractive target for cancer immunotherapy because it is overexpressed in a high proportion of many different types of tumors. However, it is also expressed in normal tissues and acts as a toleragen in vivo. Previously, detailed examination of the repertoire specific for the murine p53261–269 epitope in conventional and p53-deficient mice demonstrated that because of expression of p53, the CD8+ T cells that respond to this epitope express 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 overriding tolerance and achieving optimal activation of p53-specific CTL, the current study has assessed the effect of anti-CTLA-4 mAb on the p53-specific repertoire. It was found that blockade of CTLA-4 engagement at the time of antigenic stimulation induced a vigorous amplification of the CTL responses 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 correlated with an enhancement of helper function. However, anti-CTLA-4 treatment did not enhance the avidity of the resultant p53-specific CTL populations and, therefore, could not reverse this important consequence of tolerance.