44TiP - Inter-dependency relationships between patient-derived macrophages and circulating tumor cells in co-culture with relevance to novel therapeutic de...

Date 05 November 2016
Event ESMO Symposium on Immuno-Oncology 2016
Session Lunch and general poster viewing
Presenter Bee Luan Khoo
Citation Annals of Oncology (2016) 27 (suppl_8): viii4-viii17. 10.1093/annonc/mdw527
Authors B.L. Khoo1, W.H. Yeap2, S.C. Wong2, S.C. Lee3, C.T. Lim4, J. Han5
  • 1Biosystems And Micromechanics, Singapore MIT Alliance for Research and Technology, 138602 - Singapore/SG
  • 2Wsc Lab, Singapore Immunology Network (SIgN), Singapore/SG
  • 3Hematology-oncology, National University Cancer Institute, Singapore, Singapore/SG
  • 4Biomedical Engineering, National University of Singapore, Singapore/SG
  • 5Bioengineering, Massachusetts Institute of Technology, Boston/US

Abstract

Aim/Background

Tumors shed cancer cells, called circulating tumor cells (CTCs), into the peripheral bloodstream. Tumor progression is affected by its microenvironment, comprising both cancer cells and non-cancer cells, including macrophages. We recently developed a novel CTC Cluster Assay which mimics the tumor microenvironment in vitro. The assay promotes expansion of blood-derived primary CTCs along with macrophages differentiated directly from the same patient.

Trial design

Aim: This study aims to identify inter-dependency relationships between CTCs and macrophages to identify drug targets and monitor disease. Methods: We generate patient-derived co-cultures containing macrophages and CTCs using a microwell-based microfluidics assay. Projected cohort size is 50 samples of 10 ml blood from patients ranging from early-stage to advanced stage cancer. Blood samples are obtained via liquid biopsy (blood withdrawal), processed and maintained under hypoxic conditions to promote formation of tumor-like clusters in vitro. Macrophages differentiate directly in the assay and persist along with CTCs in culture. For evaluation of functional relationships, clusters will be sorted by magnetic pull-down assays. Cytokine panels including tumor necrosis factor (TNF), IL-1β, and other relevant factors will be tested. This study will also analyze the effects of CTC cluster formation under controlled concentrations of monocytes/macrophages. Anticipated results: Our co-culture assay allows identification of core immune factors that influence CTC cluster formation in a patient. Core factors can be modified, amplified or blocked to tip the balance towards cancer eradication. Liquid biopsy allows personalized evaluation of patients routinely throughout treatment. The efficiency of cluster formation (>70% in pre-treatment samples) allows applicability to a wide range of patient types, including early-stage cancer. Investigating interplay of key players within the tumor microenvironment has a strong potential impact to guide strategies in clinical trials, by revealing drug susceptibility or tolerance and allow immediate intervention.

Clinical trial identification

DSRB Reference 2012/00105, 2012/00979, 2010/00270, 2010/00691

Legal entity responsible for the study

Singapore Mit Alliance for Research and Technology

Funding

Singapore Mit Alliance for Research and Technology; Singapore Immunology Network (SIgN) - A Star

Disclosure

All authors have declared no conflicts of interest.