Cellular and humoral immune responses to a human pancreatic cancer antigen, coactosin-like protein, originally defined by the SEREX method

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Abstract
Among a number of human tumor antigens identified using the serological analysis of recombinant cDNA expression libraries (SEREX), only MAGE-1, tyrosinase, and NY-ESO-1 have been reported to be immunogenic tumor antigens that have the potential to elicit both humoral and cellular immunity. In this study, we determined whether our SEREX-defined pancreatic cancer antigens could be recognized by CTL, and report that one SEREX-defined antigen, coactosin-like protein (CLP), encoded cellular epitopes recognized by HLA-A2-restricted and tumor-reactive CTL. Three CLP peptides at positions 15–24, 57–65, and 104–113 possessed the ability to induce HLA-A2-restricted and tumor-reactive CTL from the PBMC of cancer patients. Subsequently, humoral responses to these peptides were investigated. IgG antibodies specific to the CLP 15–24, 57–65, and 104–113 peptides were detected in sera from 12, 0, and 12 of 12 cancer patients tested, and were also found in 5, 0, and 0 of 9 healthy donors, respectively. IgE antibodies specific to these peptides were also detected in sera from certain cancer patients and healthy donors. Since peptide-specific IgE was detected, type-I allergy to these peptides was tested. Unexpectedly the CLP 57–65 peptide, to which IgE was found in only 2 healthy donors, but not the other two peptides, was found to elicit an immediate-type hypersensitivity in all10 healthy volunteers tested. These results indicate that identical antigenic peptides can be recognized by both cellular and humoral immune systems to a tumor-associated antigen. The CLP 15–24 and104–113 peptides might be appropriate vaccine candidates for peptide-based immunotherapy of HLA-A2+ cancer patients.

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