A survey of the humoral immune response of cancer patients to a panel of human tumor antigens.
Evidence is growing for both humoral and cellular immune recognition of human tumor antigens. Antibodies with specificity for antigens initially recognized by cytotoxic T lymphocytes (CTLs), e.g., MAGE and tyrosinase, have been detected in melanoma patient sera, and CTLs with specificity for NY-ESO-1, a cancer-testis (CT) antigen initially identified by autologous antibody, have recently been identified. To establish a screening system for the humoral response to autoimmunogenic tumor antigens, an enzyme-linked immunosorbent assay (ELISA) was developed using recombinant NY-ESO-1, MAGE-1, MAGE-3, SSX2, Melan-A, and tyrosinase proteins. A survey of sera from 234 cancer patients showed antibodies to NY-ESO-1 in 19 patients, to MAGE-1 in 3, to MAGE-3 in 2, and to SSX2 in 1 patient. No reactivity to these antigens was found in sera from 70 normal individuals. The frequency of NY-ESO-1 antibody was 9.4% in melanoma patients and 12.5% in ovarian cancer patients. Comparison of tumor NY-ESO-1 phenotype and NY-ESO-1 antibody response in 62 stage IV melanoma patients showed that all patients with NY-ESO-1(+) antibody had NY-ESO-1(+) tumors, and no patients with NY-ESO-1(-) tumors had NY-ESO-1 antibody. As the proportion of melanomas expressing NY-ESO-1 is 20-40% and only patients with NY-ESO-1(+) tumors have antibody, this would suggest that a high percentage of patients with NY-ESO-1(+) tumors develop an antibody response to NY-ESO-1.
Stockert
E
E
Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, New York 10021, USA. stockere@mskcc.org
Jäger
E
E
Chen
Y T
YT
Scanlan
M J
MJ
Gout
I
I
Karbach
J
J
Arand
M
M
Knuth
A
A
Old
L J
LJ
D000912:Antibodies, Neoplasm / Q000097:blood*; D000951:Antigens, Neoplasm / Q000145:classification / Q000235:genetics / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D001943:Breast Neoplasms / Q000276:immunology; D003110:Colonic Neoplasms / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology; D058965:MART-1 Antigen; D008545:Melanoma / Q000276:immunology; D058950:Melanoma-Specific Antigens; D008565:Membrane Proteins; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000276:immunology; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology; D009369:Neoplasms / Q000276:immunology*; D010051:Ovarian Neoplasms / Q000276:immunology; D011506:Proteins / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D001323:Autoantibodies; C104948:CTAG1B protein, human; C072011:MAGEA1 protein, human; C072013:MAGEA3 protein, human; D058965:MART-1 Antigen; C548667:MLANA protein, human; D058950:Melanoma-Specific Antigens; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D011506:Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; C093962:synovial sarcoma X breakpoint proteins; D014442:Monophenol Monooxygenase