Abstract 1607: Identification of low number circulating tumor cells (CTCs) for cancer treatment monitoring

Abstract

Abstract For most solid tumors, the clinical use of CTCs is limited by current instrument restrictions on detection of infrequent CTCs. Based on the FDA-approved criteria used in current CTC detection instruments, we developed a microfluidic device capable of capturing, enumerating and releasing low numbers of CTCs in the peripheral blood of patients with solid tumors. The device is the size of a microscope slide, consisting of an inlet, an outlet, and eight parallel channels connecting them. Micromixers inside the channels enhance interactions between CTCs and capture agents on the channel surfaces. Epithelial cell-adhesion molecule (EpCAM) antibodies are immobilized onto the surfaces via avidin-biotin chemistry. A blood sample from a cancer patient is introduced through the inlet. Cells captured by anti-EpCAM studded channels are verified as CTCs using triple-color IHC definitions (EpCAM+, cytokeratin+, CD45-, and DAPI+). Using pancreatic cancer as a model for a low frequency CTC condition, device capture efficiency and cell purity was tested under various flow rates (shear stresses) using L3.6pl cells spiked into blood. Capture efficiency was defined as the% of target cells isolated relative to target cells present in a sample, representing device sensitivity. Cell purity was defined as the% of target cells isolated relative to all cells captured (both target and non-target cells), representing device specificity. Capture efficiency (90%) and cell purity (84%) were further optimized by changing the flow rate. A higher flow rate resulted in higher cell purity as non-target bound cells are dislodged by shear forces. This capability of parameter adjustment and performance control is enabled by the microfluidics platform used as opposed to CTC isolation using other commercially approved technologies. The device was then clinically tested in detecting CTCs and monitoring the response to anti-cancer drug treatment in patients with advanced pancreatic cancer. We identified CTCs in 113 out of 115 clinical blood samples (98%). CTC enumeration (CTC number/mL of blood) both correlated with and predated changes in the radiographic tumor size over the treatment period, ranging from 10 to 35 cycles (2 weeks per cycle) of therapy. Microfluidic devices possess the capacity to enumerate infrequent CTCs which also appear to correlate with treatment response. Note: This abstract was not presented at the meeting. Citation Format: Thomas J. George, Weian Sheng, Jose I. Varillas, Chen Liu, Z. Hugh Fan. Identification of low number circulating tumor cells (CTCs) for cancer treatment monitoring. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1607. doi:10.1158/1538-7445.AM2015-1607