Tn antigen is a tumor-associated antigen that appears on cancer cells as a result of aberrant O-glycosylation. The most studied form of Tn antigen is found in mucins, in particular, in mucin 1 (MUC1). Antibodies against this form of Tn antigen are used to diagnose tumors, as well as to generate T-killers with a chimeric receptor. Some carcinomas do not carry MUC1 and antibodies of a different specificity are required to detect Tn antigen on these cells. In our work, we searched for anti-Tn antibodies without preliminary assumptions about the proteins that may be carriers of the Tn antigen. For this purpose, we obtained several pairs of isogenic cell lines with the wild type and knockout of the Cosmc gene, which is essential for correct protein O-glycosylation. Using the created lines as immunogens, we generated a monoclonal antibody AKC3, which reacted with the Cosmc-deficient A549 lung adenocarcinoma cells and did not bind to the wild-type cells. Using mass spectrometry, as well as co-immunoprecipitation, it was shown that the AKC3 antibody recognized the Tn antigen in the context of CD44 protein - a protein important for tumor growth. The AKC3 antibody can be used for tumor diagnosis, and to generate T cells with a chimeric receptor for treatment of tumors that do not express mucins.

中文翻译：

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CD44 相关 Tn 抗原作为具有异常糖基化的肿瘤细胞的新生物标志物

Tn 抗原是一种肿瘤相关抗原，由于异常的 O-糖基化而出现在癌细胞上。研究最多的 Tn 抗原形式存在于粘蛋白中，尤其是粘蛋白 1 (MUC1)。针对这种形式的 Tn 抗原的抗体用于诊断肿瘤，以及产生具有嵌合受体的 T 杀伤剂。一些癌不携带 MUC1，需要不同特异性的抗体来检测这些细胞上的 Tn 抗原。在我们的工作中，我们在没有初步假设可能是 Tn 抗原载体的蛋白质的情况下寻找抗 Tn 抗体。为此，我们获得了几对具有野生型和敲除 Cosmc 基因的同基因细胞系，这对于正确的蛋白质 O-糖基化至关重要。使用创建的细胞系作为免疫原，我们生成了单克隆抗体 AKC3，它与 Cosmc 缺陷的 A549 肺腺癌细胞发生反应，但不与野生型细胞结合。使用质谱法以及免疫共沉淀，表明 AKC3 抗体在 CD44 蛋白（一种对肿瘤生长很重要的蛋白质）的背景下识别 Tn 抗原。AKC3 抗体可用于肿瘤诊断，并产生带有嵌合受体的 T 细胞，用于治疗不表达粘蛋白的肿瘤。