Angle plc, Guildford, UK, has recently announced the results of a study demonstrating a workflow for culturing circulating tumor cells (CTCs) using the company’s Parsortix system.
Undertaken at the Robert H. Lurie Comprehensive Cancer Center and the Feinberg School of Medicine at Northwestern University, the research developed an optimized workflow for the recovery and culturing of CTCs from a simple blood test to produce an effective ex vivo culture of an individual patient’s cancer cells. The research was presented in April, at the annual meeting of the American Association for Cancer Research.1
The team of investigators focused on demonstrating the capability of the system to interrogate and test cancer cells collected from patients with advanced breast cancer. According to Angle, the effort was made possible by the Parsortix system’s patented microfluidic process for CTC enrichment, which is epitope-independent (that is, it does not use antibodies) and harvests undamaged, living CTCs that can then be cultured.
“The ability to recover, culture, and interrogate cancer cells expands our possibility to advance precision medicine in breast cancer patients,” says lead researcher, Massimo Cristofanilli, MD, who is associate director of translational research at the Lurie Cancer Center and a professor of medicine at Northwestern University.
“We believe that the optimization of the workflow utilizing the Parsortix system to produce ex vivo cultures of CTCs is already opening up a new frontier in the management of breast cancer, by allowing the testing of treatments in a ‘predictive in vitro system’ truly representative of the patient’s disease, and improving our ability to select agents and predict efficacy,” says Cristofanilli. “Widely adopted, this approach has the potential to transform the way we treat cancer patients.”
According to the researchers, this is the first time that an optimized workflow for culturing CTCs ex vivo has been presented. According to company officials, growth of such cultures has been a goal of many research groups for some time, but it has not been achievable because the methods used for CTC isolation yielded low numbers of only partly purified CTCs, which were subsequently fixed (and hence killed) before isolation, damaged during the cell purification process, or irreversibly immobilized on an adherent matrix.
By contrast, the Parsortix system provides a simple and reproducible way to harvest CTCs that can be cultured—an achievement, the company notes, that cannot be accomplished by using circulating tumor DNA (ctDNA). Researchers have previously reported using the Parsortix system to culture CTCs harvested through the use of leukapheresis (transfusion of blood out of and back into the body, taking up to an hour), but this is the first time it has been achieved from a simple blood test.
For the study, the researchers tested the ex vivo culture workflow on 16 metastatic breast cancer patients. For each patient, a single 7.5 mL ethylenediaminetetraacetic acid (EDTA) blood tube was drawn. From every patient, the Parsortix system yielded viable CTCs that could be developed into an ex vivo culture. The number of CTCs harvested using the Parsortix system was significantly higher than has been reported from the use of other systems, and ranged from 300 to 17,250 CTCs per patient.
The CTCs were then cultured over a 3-week period, at the end of which the DNA was isolated and purified. The CTCs in culture retained their morphology and expanded 3.5- to 5.5-fold during week 1, and 9.5- to 22.5-fold during week 2, yielding as many as 100,000 cancer cells within 14 days, and thus providing sufficient DNA for a wide range of multiple analyses to be undertaken.
Because the mutational profile of a patient’s tumor evolves over time, a noninvasive method to provide a series of ex vivo cultures of the patient’s cancer cells for the development of organoids and in vitro drug testing enables the changing patterns of drug susceptibility in individual patients to be monitored as their tumors acquire new mutations. Such a procedure would make it more likely for the patient to receive the right drug at the right time, improving outcomes for patients and avoiding wasted resources on drugs that are ineffective.
“This is the first time that CTCs have been successfully cultured direct from a Parsortix-processed whole blood sample,” says Andrew Newland, founder and chief executive at Angle. “This work is highly encouraging for Angle. Firstly, every metastatic breast sample analyzed yielded a large number of CTCs, which is a positive sign for our FDA study. Secondly, Northwestern has achieved something that many other [cancer research centers] before them have failed to do, which is to produce an optimized workflow for reproducibly growing the CTCs. This approach is potentially applicable for every metastatic breast cancer patient, and provides another clear high-value application for Angle’s Parsortix system.”
For more information, visit Angle.
- Zhang Q, Zhang Y, Flaum L, et al. A novel ex vivo culture workflow to enrich and expand circulating tumor cells (CTCs) from patients with Stage III/IV Breast Cancer (BCa) (LB-370). Poster presented at the annual meeting of the American Association for Cancer Research, Chicago, April 14–18, 2018. Available at: https://angleplc.com/wp-content/uploads/aacr-wednesday-northwestern-18apr18-lb-370-massimo-cristofanilli.pdf. Accessed June 4, 2018.