肿瘤细胞治疗研究
英文原题：A Novel Anti-Cadherin-17 Monoclonal Antibody, Ca(17)Mab-5, for Multiple Applications.
A Novel Anti-Cadherin-17 Monoclonal Antibody, Ca(17)Mab-5, for Multiple Applications.
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Ca 17 Mab-5 是检测 CDH17 的多功能工具，具有肿瘤诊断的潜力。
Cadherin-17（CDH17，LI-cadherin）是一种非经典cadherin，具有非典型结构和独特功能。CDH17表达仅限于正常肠上皮。此外，CDH17作为一种癌蛋白，在结直肠癌、胃癌和胰腺癌中促进肿瘤迁移和侵袭。因此，CDH17是重要的诊断标志物和治疗靶点。针对CDH17的策略，包括单克隆抗体（mAbs）、双特异性抗体、抗体-药物偶联物（ADCs）和嵌合抗原受体（CAR）T细胞，已在临床前和临床研究中进行了评估。因此，开发能特异性识别细胞表面表达CDH17的mAbs对于推进肿瘤诊断和治疗至关重要。
抗人CDH17单克隆抗体（命名为Ca 17 Mabs）是通过用CDH17过表达细胞免疫小鼠并利用流式细胞术进行高通量筛选而开发的。
在Ca 17 Mabs中，一个克隆Ca 17 Mab-5（IgG 1，）通过流式细胞术特异性识别CDH17过表达的中国仓鼠卵巢-K1（CHO/CDH17）细胞，与另外21种CDH无可检测的交叉反应性。Ca 17 Mab-5还检测到人结直肠癌细胞系COLO201和COLO205中的内源性CDH17。Ca 17 Mab-5对CHO/CDH17和COLO205的表观解离常数（K D）值分别估计为1.5 10 -8 M和1.3 10 -8 M。此外，Ca 17 Mab-5通过Western blotting检测到内源性CDH17。在免疫组织化学中，Ca 17 Mab-5在正常结肠上皮、结直肠癌、胃癌和胰腺癌中表现出清晰的膜染色。
Anti-human CDH17 mAbs (named Ca 17 Mabs) were developed by immunizing a mouse with CDH17-overexpressed cells and a high-throughput screening using flow cytometry.
Among Ca 17 Mabs, a clone, Ca 17 Mab-5 (IgG 1 , ) specifically recognized CDH17-overexpressed Chinese hamster ovary-K1 (CHO/CDH17) cells with no detectable cross-reactivity to 21 other CDHs by flow cytometry. Ca 17 Mab-5 also detected endogenous CDH17 in human colorectal cancer cell lines, COLO201 and COLO205. The apparent dissociation constant ( K D ) values of Ca 17 Mab-5 for CHO/CDH17 and COLO205 were estimated as 1.5 10 -8 M and 1.3 10 -8 M, respectively. Furthermore, Ca 17 Mab-5 detected endogenous CDH17 by Western blotting. In immunohistochemistry, Ca 17 Mab-5 exhibited clear membranous staining in normal colon epithelium, colorectal, gastric, and pancreatic cancers.
Ca 17 Mab-5 is a versatile tool for detecting CDH17 and has potential for tumor diagnosis.
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