title: Antitumor efficacy of wild-type p53-specific CD4(+) T-helper cells.
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.
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, the Netherlands.
authors.forename: Sander
authors.initials: S
authors.lastname: Zwaveling
authors.forename: Michel P M
authors.initials: MP
authors.lastname: Vierboom
authors.forename: Sandra C
authors.initials: SC
authors.lastname: Ferreira Mota
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Hendriks
authors.forename: Marlies E
authors.initials: ME
authors.lastname: Ooms
authors.forename: Roger P M
authors.initials: RP
authors.lastname: Sutmuller
authors.forename: Kees L M C
authors.initials: KL
authors.lastname: Franken
authors.forename: Hans W
authors.initials: HW
authors.lastname: Nijman
authors.forename: Ferry
authors.initials: F
authors.lastname: Ossendorp
authors.forename: Sjoerd H
authors.initials: SH
authors.lastname: Van Der Burg
authors.forename: Rienk
authors.initials: R
authors.lastname: Offringa
authors.forename: Cornelis J M
authors.initials: CJ
authors.lastname: Melief
mesh_terms: 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*
chemical_list: D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments; D016159:Tumor Suppressor Protein p53