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

TLDR

Evidence is growing that both humoral and cellular immune responses recognize human tumor antigens, with antibodies against CTL‑identified antigens such as MAGE, tyrosinase, and NY‑ESO‑1 detected in melanoma patient sera. The study aimed to develop an ELISA screening system for humoral responses to autoimmunogenic tumor antigens using recombinant NY‑ESO‑1, MAGE‑1, MAGE‑3, SSX2, Melan‑A, and tyrosinase. The authors constructed an ELISA employing these recombinant proteins to detect specific antibodies. Among 234 cancer patients, antibodies were found against NY‑ESO‑1 (19/234), MAGE‑1 (3/234), MAGE‑3 (2/234), and SSX2 (1/234), none in 70 normal controls, with NY‑ESO‑1 antibody present in 9.4% of melanoma and 12.5% of ovarian cancers, and all NY‑ESO‑1+ antibody carriers had NY‑ESO‑1+ tumors, indicating a strong association between tumor expression and humoral response.

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.