Scholz D, Lubeck M, Loibner H, McDonald-Smith J, Kimoto Y, Koprowski H, Steplewski Z
Sandoz Forschungsinstitut, Vienna, Austria.
Cancer Immunol Immunother. 1991;33(3):153-7. doi: 10.1007/BF01756135.
The capacity of isotype variants of BR55-2, an anti-tumor monoclonal antibody directed against Y oligosaccharide, to mediate antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) in the human system was evaluated using freshly isolated peripheral blood mononuclear cells, lymphocytes, monocytes and complement. The ADCC activities of the BR55-2 IgG3 isotype and its switch variants (IgG1, IgG2b, and IgG2a) with human monocytes were high for all isotypes, whereas the activity of all isotypes was lower with freshly isolated lymphocytes, IgG1 being the least effective. The CDC on the other hand was strong with IgG3, IgG2b and IgG2a and negative with the IgG1 variant. The IgG3 and IgG2a isotypes were selected for further development. Their strong ADCC and CDC activity against mammary carcinoma, colon carcinoma and small-cell lung tumor cell lines was confirmed quantitatively using proteins highly purified from tissue-culture supernatants. Significant variations in ADCC and CDC competence was observed among human donors.
使用新鲜分离的外周血单核细胞、淋巴细胞、单核细胞和补体，评估了抗Y寡糖的抗肿瘤单克隆抗体BR55-2的同种型变体在人体系统中介导抗体依赖性细胞毒性（ADCC）和补体依赖性细胞毒性（CDC）的能力。BR55-2 IgG3同种型及其转换变体（IgG1、IgG2b和IgG2a）与人类单核细胞的ADCC活性在所有同种型中都很高，而所有同种型与新鲜分离的淋巴细胞的活性较低，IgG1效果最差。另一方面，IgG3、IgG2b和IgG2a的CDC较强，而IgG1变体的CDC为阴性。选择IgG3和IgG2a同种型进行进一步开发。使用从组织培养上清液中高度纯化的蛋白质，定量证实了它们对乳腺癌、结肠癌和小细胞肺癌细胞系具有很强的ADCC和CDC活性。在人类供体中观察到ADCC和CDC能力存在显著差异。
