Natali P, Bigotti A, Cavaliere R, Liao S K, Taniguchi M, Matsui M, Ferrone S
Cancer Res. 1985 Jun;45(6):2883-9.
Indirect immunofluorescence staining with a large battery of monoclonal antibodies of primary and autologous metastatic lesions removed from seven patients with melanoma has detected heterogeneity in the expression of various types of melanoma-associated antigens (MAAs), of distinct determinants of the high molecular weight melanoma-associated antigen (HMW-MAA), of the two subunits of Class I HLA antigens, and of the gene products of the HLA-D region. Among the 10 MAAs tested, the HMW-MAA had the highest frequency and the Mr 87,000 MAA the lowest. Furthermore, the HMW-MAA displayed the lowest heterogeneity. These findings, in conjunction with the restricted tissue distribution of the HMW-MAA, its lack of susceptibility to antibody-mediated modulation, and the high affinity of the available anti-HMW-MAA monoclonal antibodies, indicate that this antigen may be a useful marker for radioimaging and immunotherapy in patients with melanoma. The common acute lymphoblastic leukemia antigen was detected only in five lesions. Class I HLA antigens were detected in a larger number of lesions than HLA-DR antigens, which had a significantly higher frequency than HLA-DQ antigens. The degree of antigenic heterogeneity did not appear to correlate with the histopathological features of the lesions and/or with the clinical course of the disease. The results of the present study indicate that immunodiagnostic and immunotherapeutic approaches to melanoma should rely on the use of combinations of monoclonal antibodies to distinct MAAs.
用大量单克隆抗体对7例黑色素瘤患者切除的原发性和自体转移性病变进行间接免疫荧光染色,检测到各种类型的黑色素瘤相关抗原(MAA)、高分子量黑色素瘤相关抗原(HMW-MAA)不同决定簇、I类HLA抗原的两个亚基以及HLA-D区域基因产物的表达存在异质性。在所检测的10种MAA中,HMW-MAA出现频率最高,而分子量87,000的MAA出现频率最低。此外,HMW-MAA的异质性最低。这些发现,连同HMW-MAA受限的组织分布、其对抗体介导调节的不敏感性以及现有抗HMW-MAA单克隆抗体的高亲和力,表明该抗原可能是黑色素瘤患者放射成像和免疫治疗的有用标志物。仅在5个病变中检测到常见急性淋巴细胞白血病抗原。检测到I类HLA抗原的病变数量多于HLA-DR抗原,HLA-DR抗原的出现频率明显高于HLA-DQ抗原。抗原异质性程度似乎与病变的组织病理学特征和/或疾病的临床进程无关。本研究结果表明,黑色素瘤的免疫诊断和免疫治疗方法应依赖于使用针对不同MAA的单克隆抗体组合。