Department of Biopharmaceutical Sciences, College of Pharmacy, University of Illinois, Chicago, Illinois.
Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina.
Clin Cancer Res. 2018 Jun 1;24(11):2539-2547. doi: 10.1158/1078-0432.CCR-17-3078. Epub 2018 Mar 15.
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. 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. 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 ( = 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. 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. .
我们旨在研究多价结合和仿生细胞滚动对循环肿瘤细胞 (CTC) 捕获的敏感性和特异性的影响。我们还研究了癌症患者在接受放射治疗期间 CTC 及其动力学特征的临床意义。有组织学证实的原发性癌患者，无论是否接受化疗，都有资格入组。前瞻性地在多达五个时间点采集外周血，包括放射治疗前、治疗的第一周、中点和最后一周，以及放射治疗完成后 4 至 12 周。CTC 捕获使用基于纳米技术的测定法（CapioCyte）完成，该测定法用 EpCAM、HER-2 和 EGFR 进行了功能化。CapioCyte 能够检测到所有 24 名入组癌症患者的 CTC。多价结合通过聚（酰胺-胺）树枝状大分子进一步提高了捕获敏感性。我们还表明，细胞滚动效应可以将 CTC 捕获的特异性提高 38%（被捕获细胞中 CK/CD45/DAPI 的百分比）。在有连续 CTC 测量的 18 名患者中，中位 CTC 从放射治疗前的 113 CTCs/mL 下降到放射治疗完成时的 32 CTCs/mL（ = 0.001）。在完全临床和/或影像学反应的患者中，CTC 在放射治疗过程中持续下降，与两名已知有病理残留疾病的患者在放射治疗中期或后期 CTC 升高形成对比。我们的研究表明，与多价结合相比，多价结合和细胞滚动可以提高 CTC 捕获的敏感性和特异性，从而能够可靠地监测治疗期间和治疗后的 CTC 变化。
