The globo-series glycosphingolipids (SSEA3, SSEA4, and Globo H) were shown to express in many cancers selectively, and a combination of anti-SSEA4 and anti-Globo H antibodies was able to suppress tumor growth in mice inoculated with breast cancer cell lines. To further understand the effect, we focused on the combined effect of the two antibodies in target binding and antibody-dependent cellular cytotoxicity (ADCC) in vitro. Here, we report that the binding of anti-Globo H antibody (VK9) to MDA-MB231 breast cancer cells was influenced by anti-SSEA4 antibody (MC813–70), and a combination of both antibodies induced a similar effect as did anti-SSEA4 antibodies alone in a reporter-based ADCC assay, indicating that SSEA4 is a major target in breast cancer due to its higher expression than Globo H. Furthermore, we showed that a homogeneous anti-SSEA4 antibody (chMC813–70-SCT) designed to maximize the ADCC activity can be used to isolate a subpopulation of natural killer (NK) cells that exhibit an ∼23% increase in killing the target cells as compared to the unseparated NK cells. These findings can be used to predict a therapy outcome based on the expression levels of antigens and evaluate therapeutic antibody development.

中文翻译：

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抗 SSEA4 和抗 Globo H 抗体对乳腺癌细胞的联合作用

显示 globo 系列鞘糖脂（SSEA3、SSEA4 和 Globo H）在许多癌症中选择性表达，抗 SSEA4 和抗 Globo H 抗体的组合能够抑制接种乳腺癌细胞系的小鼠的肿瘤生长. 为了进一步了解这种效果，我们重点研究了两种抗体在体外靶标结合和抗体依赖性细胞毒性 (ADCC) 中的联合作用。在这里，我们报告抗 Globo H 抗体 (VK9) 与 MDA-MB231 乳腺癌细胞的结合受到抗 SSEA4 抗体 (MC813-70) 的影响，并且两种抗体的组合诱导了与抗-在基于报告基因的 ADCC 测定中单独使用 SSEA4 抗体，表明 SSEA4 是乳腺癌的主要靶标，因为它的表达高于 Globo H。此外，我们展示了一种旨在最大化 ADCC 活性的均质抗 SSEA4 抗体 (chMC813–70-SCT) 可用于分离自然杀伤 (NK) 细胞亚群，与相比，其杀伤靶细胞增加约 23%到未分离的 NK 细胞。这些发现可用于根据抗原的表达水平预测治疗结果并评估治疗性抗体的发展。