Cellular and humoral immune responses to a human pancreatic cancer antigen, coactosin-like protein, originally defined by the SEREX method.
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 10-113 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 all 10 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 and 104-113 peptides might be appropriate vaccine candidates for peptide-based immunotherapy of HLA-A2(+) cancer patients.
Nakatsura
Tetsuya
T
Division of Immunogenetics, Department of Neuroscience and Immunology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
Senju
Satoru
S
Ito
Masaaki
M
Nishimura
Yasuharu
Y
Itoh
Kyogo
K
D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D000912:Antibodies, Neoplasm / Q000096:biosynthesis / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D019496:Cancer Vaccines; D002461:Cell Line, Transformed; D003110:Colonic Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D018076:DNA, Complementary / Q000235:genetics; D000939:Epitopes / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007111:Immunity, Cellular; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D008840:Microfilament Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D012699:Serology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014407:Tumor Cells, Cultured
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; C118115:COTL1 protein, human; D019496:Cancer Vaccines; D018076:DNA, Complementary; D000939:Epitopes; D015789:HLA-A2 Antigen; D007074:Immunoglobulin G; D008840:Microfilament Proteins; D010446:Peptide Fragments; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D007073:Immunoglobulin E; D007371:Interferon-gamma