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Molecular characterization of PDL1 status of circulating tumor cells (CTCs) isolated with a novel label-free inertial microfluidic system from patients (pts) with advanced cancers

Date

10 Oct 2016

Session

Poster display

Presenters

Jen Fraser-Fish

Citation

Annals of Oncology (2016) 27 (6): 15-42. 10.1093/annonc/mdw363

Authors

J. Fraser-Fish1, Z. Ahmad1, R. Kumar2, B. Ebbs1, G. Fowler1, P. Flohr1, M. Crespo1, M. Ahmed2, S. Popat2, J. Bhosle2, U. Banerji3, M. O'Brien2, J.S. de Bono3, T.A. Yap3

Author affiliations

  • 1 Cancer Biomarkers Laboratory, The Institute of Cancer Research, SM2 5NG - London/GB
  • 2 Lung Cancer Unit, Royal Marsden Hospital NHS Foundation Trust, London/GB
  • 3 Drug Development Unit, Royal Marsden Hospital And Division Of Clinical Studies, The Institute of Cancer Research, London/GB
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Resources

Abstract 2357

Background

The ClearCell® FX system (FX) is a novel label-free inertial microfluidic CTC isolation platform, in contrast to the EpCAM-based CELLSEARCH® system (CS). We hypothesise that label-free CTC capture will lead to more accurate assessment of CTCs, including PD-L1 expression, and capture CTCs that have undergone epithelial-mesenchymal transition, which is prevalent in advanced cancers.

Methods

CellTrackerTM labelled EpCAM-high and EpCAM-low cell lines were spiked into healthy volunteer (HV) blood, prior to recovery on FX or CS platforms for initial validation studies. Blood samples were then obtained from pts with advanced non-small cell lung (NSCLC), prostate, ovarian, rectal and breast cancers for CTC isolation on FX and CS. CTCs captured on FX were assessed with 5-color immunofluorescence (IF) (CK, CD45, DAPI, PD-L1, as well as TTF-1 [lung adenocarcinoma], androgen receptor [AR; prostate cancer] or EpCAM [other cancers]). HV blood samples were assessed on FX and CS as controls.

Results

FX and CS captured similar counts in EpCAM-high cell lines (FX 67% ± 11 vs CS 74% ± 10 [p = 0.11]). In contrast, higher cell counts were seen with EpCAM-low cell lines with FX vs CS [62% ± 8 vs 32% ± 9 [p 

Conclusions

Higher CTC counts were isolated with FX vs CS in 86% of pts. CTC PD-L1 heterogeneity was observed and may in part explain differences in antitumor responses to PD-1/PD-L1 inhibitors. Clinical qualification of this 5-color IF PD-L1 CTC assay is ongoing in a PD-1 inhibitor NSCLC trial.

Clinical trial identification

CCR-2472 study opened 2nd August 2004 CCR-3171 study opened 22nd May 2009

Legal entity responsible for the study

The Institute of Cancer Research. The Royal Marsden Hospital

Funding

ClearBridge Biomedics

Disclosure

T.A. Yap: Funding for this research project is provided by ClearBridge Biomedics. All other authors have declared no conflicts of interest.

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