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Clin Cancer Res. 2018 Jun 1;24(11):2539-2547. doi: 10.1158/1078-0432.CCR-17-3078. Epub 2018 Mar 15.

Multivalent Binding and Biomimetic Cell Rolling Improves the Sensitivity and Specificity of Circulating Tumor Cell Capture.

Author information

1
Department of Biopharmaceutical Sciences, College of Pharmacy, University of Illinois, Chicago, Illinois.
2
Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina.
3
Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin, Madison, Wisconsin.
4
Department of Medicine, Division of Medical Oncology, Duke Cancer Institute, Duke University, Durham, North Carolina.
5
Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina. andrew_wang@med.unc.edu seungpyo.hong@wisc.edu.
6
Department of Biopharmaceutical Sciences, College of Pharmacy, University of Illinois, Chicago, Illinois. andrew_wang@med.unc.edu seungpyo.hong@wisc.edu.
7
Department of Integrated OMICs for Biomedical Science and Underwood International College, Yonsei University, Seoul, Korea.
#
Contributed equally

Abstract

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 CK+/CD45-/DAPI+) 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 = 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. Clin Cancer Res; 24(11); 2539-47. ©2018 AACR.

PMID:
29545463
PMCID:
PMC5984698
[Available on 2019-06-01]
DOI:
10.1158/1078-0432.CCR-17-3078

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