Optimization of rVAR2-Based Isolation of Cancer Cells in Blood for Building a Robust Assay for Clinical Detection of Circulating Tumor Cells

优化基于 rVAR2 的血液癌细胞分离方法,以建立可靠的循环肿瘤细胞临床检测方法

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作者:Nicolai T Sand, Tobias B Petersen, Sara R Bang-Christensen, Theresa D Ahrens, Caroline Løppke, Amalie M Jørgensen, Tobias Gustavsson, Swati Choudhary, Thor G Theander, Ali Salanti, Mette Ø Agerbæk

Abstract

Early detection and monitoring of cancer progression is key to successful treatment. Therefore, much research is invested in developing technologies, enabling effective and valuable use of non-invasive liquid biopsies. This includes the detection and analysis of circulating tumor cells (CTCs) from blood samples. Recombinant malaria protein VAR2CSA (rVAR2) binds a unique chondroitin sulfate modification present on the vast majority of cancers and thereby holds promise as a near-universal tumor cell-targeting reagent to isolate CTCs from complex blood samples. This study describes a technical approach for optimizing the coupling of rVAR2 to magnetic beads and the development of a CTC isolation platform targeting a range of different cancer cell lines. We investigate both direct and indirect approaches for rVAR2-mediated bead retrieval of cancer cells and conclude that an indirect capture approach is most effective for rVAR2-based cancer cell retrieval.

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