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Targeting altered glycosylation in secreted tumor glycoproteins for broad cancer detection.
Glycobiology ( IF 4.3 ) Pub Date : 2023-08-14 , DOI: 10.1093/glycob/cwad035
Matthew R Kudelka 1, 2 , Wei Gu 2 , Yasuyuki Matsumoto 2 , Tongzhong Ju 1 , Richard H Barnes Ii 2 , Robert J Kardish 2 , Jamie Heimburg-Molinaro 2 , Sylvain Lehoux 2 , Junwei Zeng 2 , Cynthia Cohen 3 , Brian S Robinson 3 , Kinjal S Shah 3 , Elliot L Chaikof 2 , Sean R Stowell 3 , Richard D Cummings 2
Affiliation  

There is an urgent need to develop new tumor biomarkers for early cancer detection, but the variability of tumor-derived antigens has been a limitation. Here we demonstrate a novel anti-Tn antibody microarray platform to detect Tn+ glycoproteins, a near universal antigen in carcinoma-derived glycoproteins, for broad detection of cancer. The platform uses a specific recombinant IgG1 to the Tn antigen (CD175) as a capture reagent and a recombinant IgM to the Tn antigen as a detecting reagent. These reagents were validated by immunohistochemistry in recognizing the Tn antigen using hundreds of human tumor specimens. Using this approach, we could detect Tn+ glycoproteins at subnanogram levels using cell lines and culture media, serum, and stool samples from mice engineered to express the Tn antigen in intestinal epithelial cells. The development of a general cancer detection platform using recombinant antibodies for detection of altered tumor glycoproteins expressing a unique antigen could have a significant impact on cancer detection and monitoring.

中文翻译:

针对分泌性肿瘤糖蛋白中改变的糖基化进行广泛的癌症检测。

迫切需要开发新的肿瘤生物标志物用于早期癌症检测,但肿瘤衍生抗原的变异性一直是一个限制。在这里,我们展示了一种新型抗 Tn 抗体微阵列平台,用于检测 Tn+ 糖蛋白(癌源性糖蛋白中近乎通用的抗原),用于广泛检测癌症。该平台使用针对Tn抗原(CD175)的特异性重组IgG1作为捕获试剂,并使用针对Tn抗原的重组IgM作为检测试剂。这些试剂通过免疫组织化学验证,可使用数百个人类肿瘤样本识别 Tn 抗原。利用这种方法,我们可以使用来自经过改造以在肠上皮细胞中表达 Tn 抗原的小鼠的细胞系和培养基、血清和粪便样本来检测亚纳克水平的 Tn+ 糖蛋白。使用重组抗体来检测表达独特抗原的改变的肿瘤糖蛋白的通用癌症检测平台的开发可能对癌症检测和监测产生重大影响。
更新日期:2023-05-22
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