Garin-Chesa P, Beresford H R, Carrato-Mena A, Oettgen H F, Old L J, Melamed M R, Rettig W J
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Am J Pathol. 1989 Feb;134(2):295-303.
The rapidly expanding list of monoclonal antibodies (MAbs) to human cell surface antigens provides reagents to probe the biology of malignant melanoma and to develop new diagnostic and therapeutic approaches to this disease. The criteria used to select MAb-defined antigens as targets for passive immunotherapy or immunolocalization of melanoma include: 1) consistent antigen expression in melanomas, 2) restricted antigen distribution in normal tissues and nonmelanocytic tumors, and 3) cytotoxic activity of the MAb or MAb conjugates. The present study examined the tissue distribution of three prototype melanoma cell surface antigens, the Mr 57,000 glycoprotein (gp57) recognized by MAb A42, the GD3 ganglioside, and the mel-CSPG chondroitin sulfate proteoglycan. The avidin-biotin immunoperoxidase method was used to examine a large panel of normal tissues and over 150 malignant tumors. It was found that A42 has a highly restricted distribution in normal tissues and is expressed in subsets of melanomas and nonmelanocytic tumors. It was also found that GD3 and mel-CSPG are more widely distributed in normal tissues and among tumors than was thought previously. These immunohistochemical patterns provide an essential data base to evaluate the ongoing clinical trials employing MAbs to GD3 and mel-CSPG for the therapy and immunolocalization of melanomas, and they identify gp57 as a potential marker for subsets of normal and transformed melanocytic cells.
针对人类细胞表面抗原的单克隆抗体(MAb)种类迅速增加,为探究恶性黑色素瘤的生物学特性以及开发针对该疾病的新诊断和治疗方法提供了试剂。用于选择MAb定义的抗原作为黑色素瘤被动免疫治疗或免疫定位靶点的标准包括:1)黑色素瘤中抗原表达一致;2)在正常组织和非黑色素瘤性肿瘤中抗原分布受限;3)MAb或MAb偶联物的细胞毒性活性。本研究检测了三种原型黑色素瘤细胞表面抗原的组织分布,即MAb A42识别的57,000 Mr糖蛋白(gp57)、GD3神经节苷脂和mel-CSPG硫酸软骨素蛋白聚糖。采用抗生物素蛋白-生物素免疫过氧化物酶法检测了大量正常组织和150多种恶性肿瘤。发现A42在正常组织中的分布高度受限,在黑色素瘤和非黑色素瘤性肿瘤的亚群中表达。还发现GD3和mel-CSPG在正常组织和肿瘤中的分布比以前认为的更广泛。这些免疫组织化学模式为评估目前使用针对GD3和mel-CSPG的MAb进行黑色素瘤治疗和免疫定位的临床试验提供了重要的数据库,并且它们将gp57鉴定为正常和转化的黑素细胞亚群的潜在标志物。