Kan-Mitchell J, White W L, Mitchell M S
Department of Microbiology, University of Southern California School of Medicine, Los Angeles 90033.
Cancer Res. 1989 Aug 15;49(16):4536-41.
To study tumor-associated antigens that are immunogenic to humans, we have generated human monoclonal antibodies by fusing lymph node lymphocytes of a melanoma patient with a mouse myeloma cell line. We examined in detail the reactivity of one IgG antibody, termed 2-139-1. Immunostaining was performed with purified antibody conjugated to biotin. Binding was visualized by the avidin-biotin-peroxidase complex. With cultured cells, 2-139-1 stained 12 of 12 melanomas and 12 of 16 carcinomas. Reactivity was not detectable in seven neural crest tumors, six sarcomas, and 45 lymphomas and leukemias. This spectrum of reactivity was confirmed with sections of human tissues. The human monoclonal antibody 2-139-1 reacted against melanomas and not banal nevi. While the antibody reacted strongly to adenocarcinomas of the colon, prostate, rectum, and pancreas, it did not stain all the carcinomas tested. Furthermore, reactivity was not seen against sarcomas. Interestingly, 2-139-1 did not bind to the majority of the cells in normal tissues, including fetal tissues. The reactivity of 2-139-1 may be representative of the humoral immune response found in the regional lymph nodes of cancer patients. The distribution of this epitope in various tumors was fairly limited and appeared to be associated with malignant transformation.
为了研究对人类具有免疫原性的肿瘤相关抗原，我们通过将一名黑色素瘤患者的淋巴结淋巴细胞与小鼠骨髓瘤细胞系融合，制备了人单克隆抗体。我们详细检测了一种名为2-139-1的IgG抗体的反应性。使用与生物素偶联的纯化抗体进行免疫染色。通过抗生物素蛋白-生物素-过氧化物酶复合物观察结合情况。对于培养细胞，2-139-1对12例黑色素瘤中的12例以及16例癌中的12例进行了染色。在7例神经嵴肿瘤、6例肉瘤以及45例淋巴瘤和白血病中未检测到反应性。通过人体组织切片证实了这种反应谱。人单克隆抗体2-139-1对黑色素瘤有反应，而对普通痣无反应。虽然该抗体对结肠、前列腺、直肠和胰腺的腺癌有强烈反应，但并未对所有检测的癌进行染色。此外，未观察到对肉瘤的反应性。有趣的是，2-139-1不与包括胎儿组织在内的正常组织中的大多数细胞结合。2-139-1的反应性可能代表癌症患者区域淋巴结中发现的体液免疫反应。该表位在各种肿瘤中的分布相当有限，并且似乎与恶性转化有关。
