Public Release: 

PARSORTIX cell separation system effectively isolates CTCs indicating metastatic cancer

ANGLE plc technology overcomes limitations of Ep-CAM-based cell separation approaches

Brandwidth Solutions LLC

Guildford, Surrey, UK - September 21, 2015 - Research conducted at Barts Cancer Institute, Queen Mary University, London, published today in PLOS ONE demonstrates that the Parsortix Cell Separation System from ANGLE plc, showed comparable speed - approximately two hours - in capturing circulating tumor cells (CTCs) for prostate cancer compared to bead-based epithelial cell adhesion molecule (EpCAM) antibody CTC capturing systems, while also showing improved capture of CTCs that are responsible for metastatic cancer.

The research team led by Dr. Yong-Jie Lu at Barts developed an optimized sample preparation method for the capture of CTCs from blood samples from patients with prostate cancer and healthy blood samples spiked with prostate cancer cells. Their research demonstrated that employing their method allowed the Parsortix system to process samples at a speed and sample volumes comparable to the standard CellSearch system typically used in the clinical setting, while also demonstrating the ability to harvest CTCs not only with epithelial features, but also those in the process of, or that had completed, epithelial-to-mesenchymal transition (EMT) - a significant finding that will provide more information for the detection and treatment of metastatic cancer.

"Understanding how molecular alterations in cancer cells change and evolve during cancer progression and in response to first-line therapeutics is vital to better understanding cancer progression and improving how we care for patients with metastatic disease," said Andrew Newland, CEO of ANGLE, plc. "However, current bead-based EpCAM antibody CTC capturing systems have a critical limitation. During cancer metastasis, EMT occurs to increase the invasion capability of cancer cells, which leads to the loss of epithelial markers, such as EpCAM and their replacement with mesenchymal markers. The Parsortix microfluidic system captures CTCs based on their size and deformability - not cell membrane expressed proteins - and can capture the cells that have completed EMT to allow for more precise monitoring of cancer progression."

Currently, CTC isolation is still mainly based on EpCAM expression on epithelial origin cancer cells. New research, however, indicates EMT is more and more recognized to play an important role in metastasis and that certain EMT cancer cells lose EpCAM expression. Isolation by techniques that are independent of marker expression, such as Parsortix, may help to capture those EMT CTCs.

CTC clusters have been reported to have increased metastatic potential, be more resistant to apoptosis and be correlated with poorer prognosis compared to single CTCs. In Parsortix isolated samples, the researchers also observed clusters of more than three CTCs. The ability to obtain CTC clusters will help to understand the metastasis progenitor and to predict patient prognosis.

The Barts researchers used prostate cancer as a cancer model to optimize and evaluate the Parsortix size and deformability-based system for CTC isolation and compared its efficiency with two other leading CTC systems, IsoFlux from Fluxion Biosciences and CellSearch from Janssen DX. Based on the current generally accepted definition of CTCs as CK positive, CD45 negative, nucleated and morphologically intact cells, CellSearch harvested the least CTCs among the three platforms, while the number of CTCs harvested by IsoFlux and Parsortix showed no statistically significant difference. Parsortix, however, showed significantly higher purity of harvested CTCs compared to IsoFlux, which makes downstream analysis easier.

The research also indicates that employing Parsortix can avoid potential problems in downstream analysis of CTCs caused by the magnetic beads used by CellSearch and IsoFlux.

"For example, in immunofluorescence analysis, beads adhering to the cell membrane and covering on the top of the cells prohibits effective immunostaining for membrane proteins," said lead researcher Yong-Jie Lu. "Auto-fluorescence from the beads also affects CTC analysis using fluorescence markers, such as immunofluorescence and fluorescence in situ hybridization. The bead-free systems avoid these problems in downstream CTC analysis."

"The easy to use, epitope-independent Parsortix system not only captures clinically-relevant CTCs of all different phenotypes but it allows their easy harvesting for downstream analysis. Furthermore the cells are undamaged and we have shown them to be viable for cell culture."

###

About ANGLE plc

ANGLE is a UK-based specialist medtech company commercializing the Parsortix system, a cell separation technology that enables a simple blood test to capture targeted cells, such as circulating tumor cells (CTCs) for molecular profiling and analysis. Parsortix can help deliver targeted cancer diagnostics designed to inform personalized treatment of cancer. It is also designed to be compatible with existing major medtech analytical platforms and to act as a companion diagnostic for major pharma in helping to identify patients that will benefit from a particular drug and then monitoring the drug's effectiveness. ANGLE has established formal collaborations with world-class cancer centers and is working with these cancer centers to demonstrate key applications for its Parsortix non-invasive cancer diagnostic system as a liquid biopsy. In addition to cancer cells, the Parsortix technology has the potential for deployment for other clinically significant cell types in the future.

ANGLE's Parsortix system is available for research use worldwide and is CE-IVDD Marked for indicated clinical use in Europe. The Company's first clinical application is in ovarian cancer.

ANGLE is a public company trading on the AIM market of the London Stock Exchange under the ticker symbol AGL and in the United States on the OTC-QX market under the ticker symbol ANPCY.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.