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Antitumor Efficacy of Wild-Type p53-specific CD4⁺ T-Helper Cells¹

Departments of Immunohematology and Blood Transfusion [S. Z., M. P. M. V., S. C. F. M., J. A. H., M. E. O., R. P. M. S., K. L. M. C. F., H. W. N., F. O., S. H. v. d. B., R. O., C. J. M. M.] and Surgery [S. Z.], Leiden University Medical Center, 2333 ZA Leiden, the Netherlands

Overexpression of p53 is found in 50% of human cancers, making it an attractive target antigen for immunotherapy of cancer. Research in this area has thus far primarily focused on p53-specific CTLs. Although these CTLs were shown to be highly effective against p53-overexpressing tumors in vivo, immunological tolerance seems to strongly restrict the spectrum of the p53-specific CTL repertoire in p53^+/+ subjects. In view of the emerging role of CD4⁺ Th (Th) cells in the antitumor response, we investigated the specificity and antitumor efficacy of the p53-specific Th response in mice. Our data show that high affinity Th cells against the naturally processed epitope p53^108–122 can be elicited in both p53^-/- and p53^+/+ mice, indicating that the p53-specific T-cell response is not affected by tolerance at the Th level. Furthermore, p53^108–122-specific Th cells were effective in enabling p53-specific CTLs to control the growth of p53-overexpressing tumors in vivo. Therefore, exploitation of the p53-specific Th response appears to be a highly useful aspect of immunotherapeutic strategies against cancers.

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