A Survey of the Humoral Immune Response of Cancer Patients to a Panel of Human Tumor Antigens

Abstract

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.

Expression and immunogenicity of a tumor‐associated antigen, 90K/Mac‐2 binding protein, in lung carcinoma

“…40 Also, antibodies reactive with cancer/testis antigen, such as MAGE, GAGE, BAGE, SSX, and NY-ESO-1, were found in 4.2-12.5% of sera of patients with melanoma and carcinoma of the lung, breast, and ovary. 41,42 Antibodies against mucins were elicited in 8.3% of patients with various types of cancer. 37 We have previously reported that high levels of anti-MUC4 antibodies (either IgM or IgG) are found in 29% of patients with lung carcinoma.…”

Autoantibodies against GLEA2 and PHF3 in glioblastoma: Tumor‐associated autoantibodies correlated with prolonged survival

“…9 SEREX is a powerful method to identify tumor autoantibodies in patient sera as shown for various different tumor types including glioblastoma. [9][10][11][12][13][14][15][16][17] The majority of the SEREXbased studies are aimed toward the identification of novel tumorexpressed antigens that elicit an antibody response in patients bearing the tumors. By contrast, a limited number of antigens identified by SEREX has been further characterized, most notably NY-ESO1.…”

Dominant B cell epitope from NY‐ESO‐1 recognized by sera from a wide spectrum of cancer patients: Implications as a potential biomarker

“…8 Approximately 20 -30% of the above-mentioned cancers express the protein, and moreover, nearly 40 -50% of the patients with NY-ESO-1 expressing tumors develop antibodies against the protein. 9 2) Ab titers against NY-ESO-1 are driven by antigen expression of the endogenously arising tumor, and several studies have suggested that Ab titers against NY-ESO-1 correlated with advanced stages of the antigen-positive tumor in melanoma, transitional cell carcinoma and prostate cancer. 10 -12 3) Owing to its high immunogenicity and broad expression in a variety of cancers, NY-ESO-1 has been chosen as the prototype for analysis in a number of cancer vaccine trials.…”