Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30033, United States.
Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States.
Glycobiology. 2023 Aug 14;33(7):567-578. doi: 10.1093/glycob/cwad035.
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.
目前迫切需要开发新的肿瘤生物标志物用于癌症的早期检测，但肿瘤衍生抗原的可变性一直是一个限制因素。在这里，我们展示了一种新颖的抗 Tn 抗体微阵列平台，用于检测 Tn+糖蛋白，这是一种在癌源性糖蛋白中普遍存在的近通用抗原，可广泛用于癌症检测。该平台使用针对 Tn 抗原（CD175）的特异性重组 IgG1 作为捕获试剂，以及针对 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在数百个人类肿瘤标本中识别 Tn 抗原得到了验证。使用这种方法，我们可以使用细胞系和培养基、血清和来自在肠上皮细胞中表达 Tn 抗原的基因工程小鼠的粪便样本，在亚纳克级水平检测到 Tn+糖蛋白。使用针对表达独特抗原的改变的肿瘤糖蛋白的重组抗体开发通用癌症检测平台可能会对癌症检测和监测产生重大影响。
