Circulating tumour cell (CTC)-derived organoids have the potential to provide a powerful tool for personalised cancer therapy but are restrained by low CTC numbers provided by blood samples. Here, we used diagnostic leukapheresis (DLA) to enrich CTCs from patients with metastatic prostate cancer (mPCa) and explored whether organoids provide a platform for ex vivo treatment modelling.
We prospectively screened 102 patients with mPCa and performed DLA in 40 patients with ≥5 CTCs/7.5 mL blood. We enriched CTCs from DLA using white blood cell (WBC) depletion alone or combined with EpCAM selection. The enriched CTC samples were cultured in 3D to obtain organoids and used for downstream analyses.
The DLA procedure resulted in a median yield of 5312 CTCs as compared with 22 CTCs in 7.5 mL of blood. Using WBC depletion, we recovered 46% of the CTCs, which reduced to 12% with subsequent EpCAM selection. From the isolated and enriched CTC samples, organoid expansion succeeded in 35%. Successful organoid cultures contained significantly higher CTC numbers at initiation. Moreover, we performed treatment modelling in one organoid cell line and identified substantial tumour heterogeneity in CTCs using single cell DNA sequencing.
DLA is an efficient method to enrich CTCs, although the modest success rate of culturing CTCs precludes large scale clinical application. Our data do suggest that DLA and subsequent processing provides a rich source of viable tumour cells. Therefore, DLA offers a promising alternative to biopsy procedures to obtain sufficient number of tumour cells to study sequential samples in patients with mPCa.
NL6019.
Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.
About The Expert
Lisanne Mout
Lisanne F van Dessel
Jaco Kraan
Anouk C de Jong
Rui P L Neves
Sigrun Erkens-Schulze
Corine M Beaufort
Anieta M Sieuwerts
Job van Riet
Thomas L C Woo
Ronald de Wit
Stefan Sleijfer
Paul Hamberg
Yorick Sandberg
Peter A W Te Boekhorst
Harmen J G van de Werken
John W M Martens
Nikolas H Stoecklein
Wytske M van Weerden
Martijn P Lolkema
References
PubMed