Aberrant expression of glycosphingolipids (GSLs) is a unique feature of cancer and stromal cells in tumor microenvironments. Although the impact of GSLs on tumor progression remains largely unclear, anticancer immunotherapies directed against GSLs are attracting growing attention. Here, we focus on GD2, a disialoganglioside expressed in tumors of neuroectodermal origin, and Globo H ceramide (GHCer), the most prevalent cancer‐associated GSL overexpressed in a variety of epithelial cancers. We first summarize recent advances on our understanding of GD2 and GHCer biology and then discuss the clinical development of the first immunotherapeutic agent targeting a glycolipid, the GD2‐specific antibody dinutuximab, its approved indications, and new strategies to improve its efficacy for neuroblastoma. Next, we review ongoing clinical trials on Globo H‐targeted immunotherapeutics. We end with highlighting how these studies provide sound scientific rationales for targeting GSLs in cancer and may facilitate a rational design of new GSL‐targeted anticancer therapeutics.

中文翻译：

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靶向糖鞘脂用于癌症免疫治疗

鞘糖脂 (GSL) 的异常表达是肿瘤微环境中癌症和基质细胞的独特特征。尽管 GSL 对肿瘤进展的影响仍不清楚，但针对 GSL 的抗癌免疫疗法正引起越来越多的关注。在这里，我们关注 GD2，一种在神经外胚层肿瘤中表达的双唾液酸神经节苷脂，以及 Globo H 神经酰胺（GHCer），一种在各种上皮癌中过表达的最普遍的癌症相关 GSL。我们首先总结了我们对 GD2 和 GHCer 生物学​​理解的最新进展，然后讨论了第一种针对糖脂的免疫治疗剂、GD2 特异性抗体 dinutuximab 的临床开发、其批准的适应症以及提高其对神经母细胞瘤疗效的新策略。下一个，我们回顾了正在进行的 Globo H 靶向免疫疗法的临床试验。我们最后强调这些研究如何为靶向 GSL 在癌症中提供合理的科学依据，并可能促进新的 GSL 靶向抗癌疗法的合理设计。