Purpose: We aimed to examine the effects of multivalent binding and biomimetic cell rolling on the sensitivity and specificity of circulating tumor cell (CTC) capture. We also investigated the clinical significance of CTCs and their kinetic profiles in patients with cancer undergoing radiotherapy treatment. Experimental Design: Patients with histologically confirmed primary carcinoma undergoing radiotherapy, with or without chemotherapy, were eligible for enrollment. Peripheral blood was collected prospectively at up to five time points, including before radiotherapy, at the first week, mid-point and final week of treatment, as well as 4 to 12 weeks after completion of radiotherapy. CTC capture was accomplished using a nanotechnology-based assay (CapioCyte) functionalized with aEpCAM, aHER-2, and aEGFR. Results: CapioCyte was able to detect CTCs in all 24 cancer patients enrolled. Multivalent binding via poly(amidoamine) dendrimers further improved capture sensitivity. We also showed that cell rolling effect can improve CTC capture specificity (% of captured cells that are CKþ/CD45/DAPIþ) up to 38%. Among the 18 patients with sequential CTC measurements, the median CTC decreased from 113 CTCs/mL before radiotherapy to 32 CTCs/mL at completion of radiotherapy (P ¼ 0.001). CTCs declined throughout radiotherapy in patients with complete clinical and/or radiographic response, in contrast with an elevation in CTCs at mid or post-radiotherapy in the two patients with known pathologic residual disease. Conclusions: Our study demonstrated that multivalent binding and cell rolling can improve the sensitivity and specificity of CTC capture compared with multivalent binding alone, allowing reliable monitoring of CTC changes during and after treatment.
Bibliographical noteFunding Information:
M.J. Poellmann is an employee of Capio Biosciences, Inc. T. Zhang reports receiving speakers bureau honoraria from Exelixis, is a consultant/advisory board member for AstraZeneca, Bayer, Exelixis, Genentech, Janssen, and Sanofi, and reports receiving commercial research grants from Acerta Pharma, Janssen, Merrimack, Novartis, OmniSeq, Pfizer, PGDx, and StemCentRx. A.Z. Wang is an employee of and has ownership interests (including patents) at, and reports receiving commercial research grants from Capio Biosciences. S. Hong is an employee of and has ownership interests (including patents) at, and reports receiving commercial research grants from Capio Biosciences. No potential conflicts of interest were disclosed by the other authors.
This work was supported by National Cancer Institute (NCI)/National Institutes of Health (NIH) under grant # R01-CA182528 (to S. Hong) and National Science Foundation (NSF) under grant # DMR-1409161 (to S. Hong) as well as department research fund from University of North Carolina Department of Radiation Oncology. A.Z. Wang is supported by 1R01CA178748, R21CA182322, and U54CA198999 from NIH/NCI.
All Science Journal Classification (ASJC) codes
- Cancer Research