Abstract
Circulating tumor cells (CTCs) are promising tools for risk prediction and the monitoring of response to therapy in cancer patients. Within the EU/IMI CANCER-ID consortium, we validated CTC enrichment systems for future inclusion into clinical trials. Due to the known heterogeneity of markers expressed on CTCs, we tested the Parsortix® system (ANGLE plc) which enables label-independent CTC enrichment from whole blood based on increased size and deformability of these tumor cells compared to leukocytes. We performed extensive comparisons both with spiked-in blood models (i.e., MDA-MB-468 tumor cell line cells spiked at very low concentration into blood from healthy donors) and validated the protocol on actual clinical samples from breast, lung, and gastrointestinal cancer patients to define optimal conditions for CTC enrichment. Multiple parameters including cassette gap, separation pressure, and cell fixatives were compared in parallel. Also, the compatibility of blood collection tubes with whole genome amplification of isolated tumor cells was demonstrated and we furthermore established a workflow for semi-automated CTC detection using a quantitative cell imager. The established workflow will contribute to supporting the use of size-based CTC enrichment platforms in clinical trials testing the clinical validity and utility of CTCs for personalized medicine.
| Original language | English |
|---|---|
| Article number | 442 |
| Journal | Cancers |
| Volume | 12 |
| Issue number | 2 |
| ISSN | 2072-6694 |
| DOIs | |
| Publication status | Published - 02.2020 |
Funding
Funding: Klaus Pantel received funding from the European Union-EFPIA Innovative Medicines Initiative grant CANCER-ID (Grant no. 115749), the ERC Advanced Investigator Grant INJURMET (Nr. 834974), and from an unrestricted grant of ANGLE plc (Guildford, UK). This project received funding from the European Union’s Horizon 2020 research and innovation program under Marie Sklodowska-Curie grant agreement No 765492. Klaus Pantel received funding from the European Union-EFPIA Innovative Medicines Initiative grant CANCER-ID (Grant no. 115749), the ERC Advanced Investigator Grant INJURMET (Nr. 834974), and from an unrestricted grant of ANGLE plc (Guildford, UK). This project received funding from the European Union?s Horizon 2020 research and innovation program under Marie Sklodowska-Curie grant agreement No 765492. The authors acknowledge Antje Andreas and Cornelia Coith from the University Medical Center Hamburg-Eppendorf for technical assistance. Although new EpCAM-independent CTC technologies have already shown promising results [5], standardized protocols for most approaches are still lacking. The CANCER ID consortium (www. cancer-id.eu), funded by the European Innovative Medicine Initiative (IMI), aimed to close this gap and validate innovative CTC detection approaches for future clinical trials. This standardization of novel technologies and workflows is much needed to increase the acceptance of CTCs as biomarkers in the clinic. Conflicts of Interest: Klaus Pantel has ongoing patent applications related to circulating tumor cells; his institution received research funding from European Federation of Pharmaceutical Industries and Associations (EFPIA) partners (Angle, Menarini, Agena and Servier) of the CANCER-ID programm (www.cancer-id.eu) of the European Union-EFPIA Innovative Medicines Initiative. Sonja Loges is the recipient of a Heisenberg-Professorship from the DFG (LO-1863/6-1). Sonja Loges and Melanie Janning receive funding from the Margarethe-Clemens Stiftung. The remaining authors declare no conflict of interest.
Research Areas and Centers
- Research Area: Luebeck Integrated Oncology Network (LION)
- Centers: University Cancer Center Schleswig-Holstein (UCCSH)
