An Engineered Human Fc-Mannose-Binding-Lectin Captures Circulating Tumor Cells

Abstract

Tumor cells circulating throughout the body have shown great potential for providing new diagnostic or therapeutic strategies for treating cancer patients. However, isolating circulating tumor cells (CTCs) is still challenging due to the lack of broad spectrum reagents that bind specifically to these cells. This study shows that an engineered human blood opsonin that mimics the innate immune mechanism for opsonizing complex mannan carbohydrates, Fc-mannose binding lectin (FcMBL), exhibits a broad spectrum of CTC binding activity. Using FcMBL-coated magnetic beads, this study is able to specifically capture and isolate a broad range of tumor cells spiked into buffer or blood. FcMBL is bound preferentially to human and mouse breast cancer cells relative to normal breast epithelium, and this study demonstrates the capture of seven different types of cancer cells with greater than 90% capture efficiency, whereas two of these same cancer cells bound poorly to anti epithelial cell adhesion molecule antibodies. It is also confirmed that FcMBL-coated magnetic beads can be used to capture CTCs from the blood of mice bearing metastatic tumors. The FcMBL capture technology may therefore provide a new tool for harvesting a broad range of CTCs with high efficiency as it targets tumor cell specific surface markers that are expressed across diverse cell types and retained throughout the metastatic process.