Editors' ChoiceCancer

Continuously capturing circulating cancer cells

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Science Translational Medicine  24 Apr 2019:
Vol. 11, Issue 489, eaax1730
DOI: 10.1126/scitranslmed.aax1730

Abstract

A wearable apheresis device allows for continuous and specific capture of circulating tumor cells.

Liquid biopsies hold promise to assist with accurate and timely cancer diagnosis and to identify evolutionary changes earlier. With the rise of molecularly targeted therapies, liquid biopsies may also help predict tumor response to treatment. However, the scarcity of tumor-derived materials within blood is one major limitation that has restricted the utility of liquid biopsies. Circulating tumor cells (CTCs) shed from primary or metastatic foci are exceedingly rare: ~1-5 cells per milliliter of blood. Most current CTC capture tests rely on one-time sampling of up to 10 ml of blood, resulting in few cells for analysis. There is a need for methods that can sample larger volumes of blood to capture more CTCs.

One promising strategy uses apheresis to increase CTC yield. Apheresis involves blood removal, separation of cells of interest, followed by reinfusion of the blood. However, commercial apheresis units were designed to filter white blood cells but not CTCs; they are also bulky. To overcome these limitations, Kim et al. describe a novel intravascular system specifically designed for CTC capture that uses a wearable apheresis device. CTCs are captured using the integrated herringbone graphene oxide chip (HBGO chip) with immobilized antibodies against epithelial cellular adhesion molecule protein (EpCAM) while other blood elements return to the patient’s circulation. All system components were sterilized, and procedures were implemented to minimize blood clotting. The authors tested this device by infusing human cancer cell lines into canine models. They were able to sample blood continuously for up to two hours, adding extra HBGO chips upon saturation. The dogs had no noticeable symptoms from collection. This device could screen ~2% of the dogs’ total blood volume in two hours (total of 1 L compared with 5 L for humans), achieving a greater CTC yield than serial blood draws. Strategies to increase flow rate for increased throughput, which will be necessary for implementation in humans, are under way.

This work demonstrates the feasibility of implementing a portable, minimally invasive, self-contained system to continuously isolate CTCs. There are several limitations, including that the animal model did not test endogenous cancer, the device only used EpCAM capture antibodies, and the device has not yet been tested in humans. Evaluating the system with a wider variety of tumors and capture antibodies, increasing its throughput, and testing with human subjects will be critical before implementation in translational and clinical settings.

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