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Specific killing of P53 mutated tumor cell lines by a cross‐reactive human HLA‐A2‐restricted P53‐specific CTL line
Author(s) -
Würtzen Peter A.,
Pedersen Lars Ø.,
Poulsen Hans S.,
Claesson Mogens H.
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.1417
Subject(s) - ctl* , epitope , biology , clone (java method) , cytotoxic t cell , human leukocyte antigen , cell culture , cd8 , cancer research , immunology , immunotherapy , antigen , microbiology and biotechnology , in vitro , immune system , genetics , gene
p53 is upregulated in the majority of spontaneous tumors and the HLA class I molecule HLA‐A2 is expressed by approximately 50% of the caucasians. Potentially, these facts make HLA‐A2‐binding p53 peptides for CTL‐inducing immunotherapy applicable to a broad range of cancer patients. In our study, we investigated the CTL‐inducing capacity of autologous monocyte‐derived dendritic cells (DC) maturated by exposure to CD40L and pulsed with a pool of 4 wild‐type, HLA‐A2‐binding p53 peptides, and the p53‐specific CD8 + CTL lines established from healthy HLA‐A2‐positive donors were characterized. Reactivity to p53 65–73 and p53 187–197 peptides was obtained in the T‐cell lines. Interestingly, cold target inhibition experiments demonstrated that the simultaneous recognition of the 2 peptides was the result of cross‐reactivity, which was confirmed by killing experiments at the clonal CTL level. Furthermore, 4 HLA‐A2 + p53‐mutated tumor cell lines were lysed by the CTL line, indicating that these peptides are endogenously processed and presented on HLA‐A2 molecule. Thus, monocyte‐derived DC pulsed with a pool of peptides are able to induce CTL reactivity to wild‐type p53 peptides presented by several cancer cell lines. In addition, the recognition of 2 different p53 peptides by the same CTL clone suggests a promiscuous peptide recognition by the TCR involved. Taken together, these in vitro results suggest that vaccination with autologous DC pulsed with multiple p53 epitopes may induce an effective tumor‐specific CTL response in vivo with the potential to eradicate p53‐upregulated spontaneously occurring tumors. © 2001 Wiley‐Liss, Inc.