Hoon D S, Wang Y, Sze L, Kanda H, Watanabe T, Morrison S L, Morton D L, Irie R F
John Wayne Institute for Cancer Treatment and Research, Santa Monica, California 90404.
Cancer Res. 1993 Nov 1;53(21):5244-50.
In this study we report the characterization of a human monoclonal antibody (HuMab), L612, that reacts with ganglioside GM3 and has therapeutic application for the treatment of human neoplasms, particularly melanoma. A permanent IgM-secreting Epstein-Barr virus-transformed B-cell line L612 was established. L612 HuMab bound specifically to neoplastic cell lines in culture and in tissue biopsy specimens such as melanoma, colon, breast, and lung cancer. The antibody did not bind to normal cells or biopsy tissue. HuMab L612 showed the highest reactivity to melanoma cells, particularly to those with high concentrations of GM3. Immunostaining on high-performance thin-layer chromatography plates demonstrated that L612 HuMab bound to GM3 purified from melanoma cells. Removal of the sialic acid from GM3 abolished antibody binding. HuMab L612 also reacted to GM4 purified from egg yolk, indicating that it recognizes an NeuAc alpha 2-3 galactose antigen determinant. HuMab L612 heavy and light chains were sequenced and determined to belong to the mu heavy chain variable subgroup III and kappa chain variable subgroup IV families, respectively. The studies indicate that the L612 HuMab has significant therapeutic potential for a wide variety of human cancers.
在本研究中，我们报告了一种人单克隆抗体（HuMab）L612的特性，该抗体与神经节苷脂GM3反应，并具有治疗人类肿瘤尤其是黑色素瘤的应用价值。建立了一个永久性分泌IgM的爱泼斯坦-巴尔病毒转化的B细胞系L612。L612 HuMab在培养物中和组织活检标本（如黑色素瘤、结肠癌、乳腺癌和肺癌）中与肿瘤细胞系特异性结合。该抗体不与正常细胞或活检组织结合。HuMab L612对黑色素瘤细胞表现出最高的反应性，尤其是对那些GM3浓度高的细胞。在高效薄层层析板上的免疫染色表明，L612 HuMab与从黑色素瘤细胞中纯化的GM3结合。从GM3上去除唾液酸消除了抗体结合。HuMab L612也与从蛋黄中纯化的GM4反应，表明它识别NeuAcα2-3半乳糖抗原决定簇。对HuMab L612的重链和轻链进行了测序，确定它们分别属于μ重链可变亚组III和κ链可变亚组IV家族。这些研究表明，L612 HuMab对多种人类癌症具有显著的治疗潜力。
