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Brief Definitive Reports

Elisabeth Stockert^*, Elke Jäger, Yao-Tseng Chen^*,, Matthew J. Scanlan^*, Ivan Gout^||, Julia Karbach, Michael Arand^¶, Alexander Knuth, and Lloyd J. Old^*

From the ^* Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, New York 10021; II. Medizinische Klinik, Hämatologie–Onkologie, Krankenhaus Nordwest, 60488 Frankfurt, Germany; the Cornell University Medical College, New York 10021; ^|| Ludwig Institute for Cancer Research, London Branch at University College London School of Medicine, W1P 8BT London, United Kingdom; and the ^¶ Institut für Toxikologie, Johannes Gutenberg Universität, 55131 Mainz, Germany

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.

This work was partially funded by National Institutes of Health grant CA-68024.

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