Abstract B45: High-throughput label-free isolation and expansion of circulating tumor cells (CTCs) from non-small cell lung cancer (NSCLC) patients for personalized treatments

Abstract

Abstract Background: Circulating tumor cell (CTC) clusters are emerging as clinically significant harbingers of metastases in solid organ cancers. Prior to engaging these CTC clusters in animal models of metastases, it is imperative for technology to identify them with high sensitivity. These clusters often present heterogeneous surface markers, and current methods for isolation of clusters may fall short. Methods: We have applied the inertial microfluidic Labyrinth device for high-throughput, biomarker-independent, size-based isolation of CTCs and CTC clusters from patients with metastatic non-small cell lung cancer (NSCLC). Results: Using the Labyrinth device, CTCs (PanCK+/DAPI+/CD45-) were isolated from metastatic NSCLC patients (n=25). Heterogeneous CTC populations were detected, including CTCs expressing epithelial (EpCAM), mesenchymal (vimentin), or both markers. CTCs were isolated from 100% of patients (417±1023 CTCs/mL), and CTCs that were EpCAM negative were significantly higher in numbers than EpCAM+ CTCs. Cell clusters of ≥2 CTCs were observed in 96% of patients, of which 75% were negative for EpCAM. Patients with higher number of CTC clusters than single CTCs had worse progression-free survival (PFS) (p=0.05). Recovered CTCs from patients with RET, ROS1, and ALK-rearranged tumors revealed identical genetic aberrations as the primary tumor for each gene using FISH analysis. We have successfully expanded the recovered CTCs from 2 patients and screened for therapeutic targeting. We have found that TPX-0005 might be effective in these patients and would direct them to a clinical trial using this compound. Conclusions: The label-free Labyrinth device demonstrated the capability of collecting recovered CTCs from the device using a continuous processing technique while in a suspension state. This advantage opens the opportunities not only for CTC expansion off-chip, but also for ex vivo drug testing to direct patient-specific therapies. Citation Format: Mina Zeinali, Wei Huang, Maggie Lee, Arthi Nadhan, Anvya Mathur, Casey Hedman, Eric Lin, Ramdane Harouaka, Max S. Wicha, Lili Zhao, Nallasivam Palanisamy, Mathias Hafner, Rishindra Reddy, Gregory P. Kalemkerian, Bryan J. Schneider, Khaled A. Hassan, Nithya Ramnath, Sunitha Nagrath. High-throughput label-free isolation and expansion of circulating tumor cells (CTCs) from non-small cell lung cancer (NSCLC) patients for personalized treatments [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr B45.