Antitumor efficacy of wild-type p53-specific CD4(+) T-helper cells.
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.
Zwaveling
Sander
S
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, the Netherlands.
Vierboom
Michel P M
MP
Ferreira Mota
Sandra C
SC
Hendriks
Jennifer A
JA
Ooms
Marlies E
ME
Sutmuller
Roger P M
RP
Franken
Kees L M C
KL
Nijman
Hans W
HW
Ossendorp
Ferry
F
Van Der Burg
Sjoerd H
SH
Offringa
Rienk
R
Melief
Cornelis J M
CJ
D000595:Amino Acid Sequence; D000818:Animals; D003713:Dendritic Cells / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D016219:Immunotherapy, Adoptive; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy; D010446:Peptide Fragments / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments; D016159:Tumor Suppressor Protein p53