1. Antitumor efficacy of wild-type p53-specific CD4(+) T-helper cells.
- Author
-
Zwaveling S, Vierboom MP, Ferreira Mota SC, Hendriks JA, Ooms ME, Sutmuller RP, Franken KL, Nijman HW, Ossendorp F, Van Der Burg SH, Offringa R, and Melief CJ
- Subjects
- Amino Acid Sequence, Animals, Dendritic Cells immunology, Epitopes, T-Lymphocyte immunology, Female, Immunotherapy, Adoptive, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Mice, Nude, Molecular Sequence Data, Neoplasms, Experimental immunology, Neoplasms, Experimental therapy, Peptide Fragments immunology, T-Lymphocytes, Cytotoxic immunology, Transfection, Tumor Suppressor Protein p53 genetics, T-Lymphocytes, Helper-Inducer immunology, Tumor Suppressor Protein p53 immunology
- Abstract
Overexpression of p53 is found in approximately 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.
- Published
- 2002