The stage-specific embryonic antigen-4 (SSEA-4) is a cell surface glycosphingolipid antigen expressed in early stages of human development. This surface marker is downregulated during the differentiation process but is found re-expressed in several types of tumors, including breast cancer. This feature makes SSEA-4 an attractive target for the development of therapeutic antibodies against tumors. In this work, we first studied the binding and intracellular fate of the monoclonal antibody MC-813-70 directed against SSEA-4. MC-813-70 was found to be rapidly internalized into triple-negative breast cancer cells following binding to its target at the plasma membrane, and to accumulate in acidic organelles, most likely lysosomes. Given the internalization feature of MC-813-70, we next tested whether the antibody was able to selectively deliver the saporin toxin inside SSEA-4-expressing cells. Results show that the immunotoxin complex was properly endocytosed and able to reduce cell viability of breast cancer cells in vitro, either alone or in combination with chemotherapeutic drugs. Our findings indicate that the MC-813-70 antibody has the potential to be developed as an alternative targeted therapeutic agent for cancer cells expressing the SSEA-4 glycolipid.

中文翻译：

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利用针对糖鞘脂SSEA-4的抗体的内在化特征在乳腺癌细胞中递送免疫毒素。

阶段特异性胚胎抗原-4（SSEA-4）是在人类发育早期表达的细胞表面糖鞘脂抗原。该表面标志物在分化过程中被下调，但在包括乳腺癌在内的几种类型的肿瘤中被重新表达。该特征使SSEA-4成为开发针对肿瘤的治疗性抗体的有吸引力的靶标。在这项工作中，我们首先研究了针对SSEA-4的单克隆抗体MC-813-70的结合和细胞内命运。发现MC-813-70与质膜上的靶标结合后会迅速内化为三阴性乳腺癌细胞，并积聚在酸性细胞器中，最可能是溶酶体。鉴于MC-813-70的内部化功能，接下来，我们测试了该抗体是否能够选择性地在表达SSEA-4的细胞内递送血红素毒素。结果表明，无论是单独使用还是与化学治疗药物联合使用，免疫毒素复合物均能被适当地内吞并能够降低乳腺癌细胞的细胞活力。我们的发现表明，MC-813-70抗体有潜力被开发为表达SSEA-4糖脂的癌细胞的替代靶向治疗剂。