Wang Denong, Wu Lisa, Liu Xiaohe
Tumor Glycomics Laboratory, Biosciences Division, SRI International, 333 Ravenswood Avenue, Menlo Park, CA, 94025-3493, USA.
Biosciences Division, SRI International, 333 Ravenswood Avenue, Menlo Park, CA, 94025-3493, USA.
Adv Exp Med Biol. 2017;994:275-284. doi: 10.1007/978-3-319-55947-6_15.
We present here an experimental approach for exploring a new class of tumor biomarkers that are overexpressed by circulating tumor cells (CTCs) and are likely targetable in immunotherapy against tumor metastasis. Using carbohydrate microarrays, anti-tumor monoclonal antibodies (mAbs) were scanned against a large panel of carbohydrate antigens to identify potential tumor glycan markers. Subsequently, flow cytometry and fiber-optic array scanning technology (FAST) were applied to determine whether the identified targets are tumor-specific cell-surface markers and are, therefore, likely suitable for targeted immunotherapy. Finally, the tumor glycan-specific antibodies identified were validated using cancer patients' blood samples for their performance in CTC-detection and immunotyping analysis. In this article, identifying breast CTC-specific glycan markers and targeting mAbs serve as examples to illustrate this tumor biomarker discovery strategy.
我们在此展示一种实验方法,用于探索一类新的肿瘤生物标志物,这些标志物由循环肿瘤细胞(CTC)过表达,并且在针对肿瘤转移的免疫治疗中可能成为可靶向的目标。利用碳水化合物微阵列,针对大量碳水化合物抗原扫描抗肿瘤单克隆抗体(mAb),以识别潜在的肿瘤聚糖标志物。随后,应用流式细胞术和光纤阵列扫描技术(FAST)来确定所识别的靶点是否为肿瘤特异性细胞表面标志物,因此是否可能适用于靶向免疫治疗。最后,使用癌症患者的血样对所识别的肿瘤聚糖特异性抗体在CTC检测和免疫分型分析中的性能进行验证。在本文中,鉴定乳腺CTC特异性聚糖标志物和靶向单克隆抗体作为示例来说明这种肿瘤生物标志物发现策略。