Multivalent binding and biomimetic cell rolling improves the sensitivity and specificity of circulating tumor cell capture

Ja Hye Myung, Michael J. Eblan, Joseph M. Caster, Sin Jung Park, Michael J. Poellmann, Kyle Wang, Kevin A. Tam, Seth M. Miller, Colette Shen, Ronald C. Chen, Tian Zhang, Joel E. Tepper, Bhishamjit S. Chera, Andrew Z. Wang, Seungpyo Hong

Research output: Contribution to journalArticle

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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 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.

Original languageEnglish
Pages (from-to)2539-2547
Number of pages9
JournalClinical Cancer Research
Volume24
Issue number11
DOIs
Publication statusPublished - 2018 Jun 1

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Circulating Neoplastic Cells
Biomimetics
Radiotherapy
Sensitivity and Specificity
Dendrimers
Nanotechnology
Neoplasms
Research Design
Therapeutics
Carcinoma
Drug Therapy

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Myung, Ja Hye ; Eblan, Michael J. ; Caster, Joseph M. ; Park, Sin Jung ; Poellmann, Michael J. ; Wang, Kyle ; Tam, Kevin A. ; Miller, Seth M. ; Shen, Colette ; Chen, Ronald C. ; Zhang, Tian ; Tepper, Joel E. ; Chera, Bhishamjit S. ; Wang, Andrew Z. ; Hong, Seungpyo. / Multivalent binding and biomimetic cell rolling improves the sensitivity and specificity of circulating tumor cell capture. In: Clinical Cancer Research. 2018 ; Vol. 24, No. 11. pp. 2539-2547.
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title = "Multivalent binding and biomimetic cell rolling improves the sensitivity and specificity of circulating tumor cell capture",
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{\th}/CD45/DAPI{\th}) 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.",
author = "Myung, {Ja Hye} and Eblan, {Michael J.} and Caster, {Joseph M.} and Park, {Sin Jung} and Poellmann, {Michael J.} and Kyle Wang and Tam, {Kevin A.} and Miller, {Seth M.} and Colette Shen and Chen, {Ronald C.} and Tian Zhang and Tepper, {Joel E.} and Chera, {Bhishamjit S.} and Wang, {Andrew Z.} and Seungpyo Hong",
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Myung, JH, Eblan, MJ, Caster, JM, Park, SJ, Poellmann, MJ, Wang, K, Tam, KA, Miller, SM, Shen, C, Chen, RC, Zhang, T, Tepper, JE, Chera, BS, Wang, AZ & Hong, S 2018, 'Multivalent binding and biomimetic cell rolling improves the sensitivity and specificity of circulating tumor cell capture', Clinical Cancer Research, vol. 24, no. 11, pp. 2539-2547. https://doi.org/10.1158/1078-0432.CCR-17-3078

Multivalent binding and biomimetic cell rolling improves the sensitivity and specificity of circulating tumor cell capture. / Myung, Ja Hye; Eblan, Michael J.; Caster, Joseph M.; Park, Sin Jung; Poellmann, Michael J.; Wang, Kyle; Tam, Kevin A.; Miller, Seth M.; Shen, Colette; Chen, Ronald C.; Zhang, Tian; Tepper, Joel E.; Chera, Bhishamjit S.; Wang, Andrew Z.; Hong, Seungpyo.

In: Clinical Cancer Research, Vol. 24, No. 11, 01.06.2018, p. 2539-2547.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Multivalent binding and biomimetic cell rolling improves the sensitivity and specificity of circulating tumor cell capture

AU - Myung, Ja Hye

AU - Eblan, Michael J.

AU - Caster, Joseph M.

AU - Park, Sin Jung

AU - Poellmann, Michael J.

AU - Wang, Kyle

AU - Tam, Kevin A.

AU - Miller, Seth M.

AU - Shen, Colette

AU - Chen, Ronald C.

AU - Zhang, Tian

AU - Tepper, Joel E.

AU - Chera, Bhishamjit S.

AU - Wang, Andrew Z.

AU - Hong, Seungpyo

PY - 2018/6/1

Y1 - 2018/6/1

N2 - 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.

AB - 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.

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DO - 10.1158/1078-0432.CCR-17-3078

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EP - 2547

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

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