Stockert E, Jäger E, Chen Y T, Scanlan M J, Gout I, Karbach J, Arand M, Knuth A, Old L J
Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, New York 10021, USA.
J Exp Med. 1998 Apr 20;187(8):1349-54. doi: 10.1084/jem.187.8.1349.
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.
越来越多的证据表明，人体肿瘤抗原可被体液免疫和细胞免疫识别。在黑色素瘤患者血清中已检测到对最初由细胞毒性T淋巴细胞（CTL）识别的抗原具有特异性的抗体，例如MAGE和酪氨酸酶，并且最近已鉴定出对NY-ESO-1具有特异性的CTL，NY-ESO-1是一种最初由自体抗体鉴定出的癌胚（CT）抗原。为了建立针对自身免疫原性肿瘤抗原的体液反应筛选系统，使用重组NY-ESO-1、MAGE-1、MAGE-3、SSX2、Melan-A和酪氨酸酶蛋白开发了一种酶联免疫吸附测定（ELISA）。对234名癌症患者的血清进行的调查显示，19名患者体内有抗NY-ESO-1抗体，3名患者体内有抗MAGE-1抗体，2名患者体内有抗MAGE-3抗体，1名患者体内有抗SSX2抗体。在70名正常个体的血清中未发现对这些抗原的反应性。NY-ESO-1抗体在黑色素瘤患者中的频率为9.4%，在卵巢癌患者中为12.5%。对62名IV期黑色素瘤患者的肿瘤NY-ESO-1表型和NY-ESO-1抗体反应进行比较，结果显示，所有具有NY-ESO-1(+)抗体的患者均有NY-ESO-1(+)肿瘤，而没有NY-ESO-1(-)肿瘤的患者有NY-ESO-1抗体。由于表达NY-ESO-1的黑色素瘤比例为20%-40%，且只有NY-ESO-1(+)肿瘤的患者才有抗体，这表明NY-ESO-1(+)肿瘤的患者中有很大比例会产生针对NY-ESO-1的抗体反应。
