Research demonstrates Parsortix workflow for culturing circulating tumour cells for in-vitro drug testing
The research was undertaken by the Robert H Lurie Comprehensive Cancer Centre and the Feinberg School of Medicine, Northwestern University, Chicago (Northwestern)
Unique capabilities of ANGLE’s Parsortix system address a key aim of precision medicine to test drugs outside the patient to determine which drugs will benefit the patient Work highlights another major opportunity for the use of ANGLE’s Parsortix system in breast cancer post FDA clearance
ANGLE plc, a liquid biopsy company, announced that results presented by one of the leading US cancer centres at the American Association for Cancer Research conference (AACR) 2018, in Chicago have demonstrated a workflow for culturing circulating tumor cells (CTCs) using ANGLE’s ParsortixTM system. The research undertaken by the Robert H Lurie Comprehensive Cancer Centre and the Feinberg School of Medicine, Northwestern University, Chicago (Northwestern) has developed an optimised workflow for the recovery and culturing of CTCs from a simple blood test to produce an effective ex-vivo culture (cells growing outside the patient) of the individual patient’s cancer cells.
The team of investigators led by Dr Massimo Cristofanilli focussed on demonstrating the capability to interrogate and test cancer cells collected from patients with advanced breast cancer. This was only possible because the epitope-independent (does not use antibodies) patented microfluidic process used by the Parsortix system for CTC enrichment harvests undamaged living CTCs, which can then be cultured. Reportedly, this is the first time that an optimised workflow has been presented to culture CTCs ex-vivo. This has been a goal of many research groups for some time but has not been achievable because the methods of CTC isolation used yield low numbers of only partially purified CTCs that are fixed before isolation (hence killed), damaged during the cell purification process, or irreversibly immobilised on an adherent matrix.
The Parsortix system neatly avoids all these problems providing a simple reproducible way to harvest CTCs that can be cultured. This is another example of the use of CTCs harvested using the Parsortix system, which cannot be addressed using ctDNA. Previous culturing of CTCs harvested from leukapheresis (transfusion of blood out and back into the body taking up to an hour) product using Parsortix has been reported but this is the first time it has been achieved from a simple blood test. Northwestern tested their ex-vivo culture workflow on 16 metastatic breast cancer patients. A single 7.5ml EDTA blood tube was drawn from a simple blood test for each patient. In every patient (100 per cent), 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 with other systems and ranged from 300 to 17,250 CTCs per patient. The CTCs were then successfully cultured over a three week period at which time the DNA was isolated and purified. The CTCs in culture retained their morphology and expanded 3.5 – 5.5 fold in week one, and then 9.5 – 22.5 fold in week two yielding as many as 100,000 cancer cells within 14 days thus providing sufficient DNA for a wide range of multiple analyses to be undertaken.
Northwestern’s poster presentation to AACR 2018 is entitled “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)”. Consequently a non-invasive method to provide a series of ex-vivo cultures of the patient’s cancer cells for organoids development and in-vitro drug testing enables the changing patterns of drug susceptibility in individual patients to be monitored as their tumours acquire new mutations. This would enable the patient to receive the right drug at the right time, improving outcomes for patients and avoiding wasted resources on drugs, which are ineffective. Professor Massimo Cristofanilli, MD Associate Director, Translational Research – Robert H Lurie Comprehensive Cancer Centre, Northwestern University, commented, “The ability to recover, culture and interrogate cancer cells expands our possibility to advance precision medicine in breast cancer patients. We believe that the optimisation of the workflow utilising 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. Widely adopted, this approach has the potential to transform the way we treat cancer patients.”
Andrew Newland, ANGLE Founder and Chief Executive, commented, “This is the first time that CTCs have been successfully cultured direct from a Parsortix processed whole blood sample. This work is highly encouraging for ANGLE. Firstly every metastatic breast sample analysed yielded a large number of CTCs, which is a positive sign for our FDA study. Secondly, Northwestern has achieved something that many other Centres before them have failed to do, which is to produce an optimised 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.”
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