Research conductedat Barts Cancer Institute, Queen Mary University, London, published today inPLOS ONE demonstrates that the Parsortix Cell Separation System from ANGLE plc,showed comparable speed – approximately two hours – in capturing circulatingtumor cells (CTCs) for prostate cancer compared to bead-based epithelial celladhesion molecule (EpCAM) antibody CTC capturing systems, while also showingimproved capture of CTCs that are responsible for metastatic cancer.

“Understanding how molecularalterations in cancer cells change and evolve during cancer progression and inresponse to first-line therapeutics is vital to better understanding cancerprogression and improving how we care for patients with metastatic disease”

The research teamled by Dr. Yong-Jie Lu at Barts developed an optimized sample preparationmethod for the capture of CTCs from blood samples from patients with prostatecancer and healthy blood samples spiked with prostate cancer cells. Theirresearch demonstrated that employing their method allowed the Parsortix systemto process samples at a speed and sample volumes comparable to the standardCellSearch system typically used in the clinical setting, while alsodemonstrating 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 willprovide more information for the detection and treatment of metastatic cancer.

“Understanding howmolecular alterations in cancer cells change and evolve during cancerprogression and in response to first-line therapeutics is vital to betterunderstanding cancer progression and improving how we care for patients withmetastatic disease,” said Andrew Newland, CEO of ANGLE, plc. “However, currentbead-based EpCAM antibody CTC capturing systems have a critical limitation.During cancer metastasis, EMT occurs to increase the invasion capability ofcancer cells, which leads to the loss of epithelial markers, such as EpCAM andtheir replacement with mesenchymal markers. The Parsortix microfluidic systemcaptures CTCs based on their size and deformability – not cell membraneexpressed proteins – and can capture the cells that have completed EMT to allowfor more precise monitoring of cancer progression.”

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

CTC clusters havebeen reported to have increased metastatic potential, be more resistant toapoptosis and be correlated with poorer prognosis compared to single CTCs. InParsortix isolated samples, the researchers also observed clusters of more thanthree CTCs. The ability to obtain CTC clusters will help to understand themetastasis progenitor and to predict patient prognosis.

The Bartsresearchers used prostate cancer as a cancer model to optimize and evaluate theParsortix size and deformability-based system for CTC isolation and comparedits efficiency with two other leading CTC systems, IsoFlux from FluxionBiosciences and CellSearch from Janssen DX. Based on the current generallyaccepted definition of CTCs as CK positive, CD45 negative, nucleated andmorphologically intact cells, CellSearch harvested the least CTCs among thethree platforms, while the number of CTCs harvested by IsoFlux and Parsortixshowed no statistically significant difference. Parsortix, however, showedsignificantly higher purity of harvested CTCs compared to IsoFlux, which makesdownstream analysis easier.

The research alsoindicates that employing Parsortix can avoid potential problems in downstreamanalysis of CTCs caused by the magnetic beads used by CellSearch and IsoFlux.

“For example, inimmunofluorescence analysis, beads adhering to the cell membrane and coveringon the top of the cells prohibits effective immunostaining for membraneproteins,” said lead researcher Yong-Jie Lu. “Auto-fluorescence from the beadsalso affects CTC analysis using fluorescence markers, such asimmunofluorescence and fluorescence in situ hybridization. The bead-freesystems avoid these problems in downstream CTC analysis.”

“The easy to use,epitope-independent Parsortix system not only captures clinically-relevant CTCsof all different phenotypes but it allows their easy harvesting for downstreamanalysis. Furthermore the cells are undamaged and we have shown them to beviable for cell culture.”

AboutANGLE plc

ANGLE is aUK-based specialist medtech company commercializing the Parsortix system, acell separation technology that enables a simple blood test to capture targetedcells, such as circulating tumor cells (CTCs) for molecular profiling andanalysis. Parsortix can help deliver targeted cancer diagnostics designed toinform personalized treatment of cancer. It is also designed to be compatiblewith existing major medtech analytical platforms and to act as a companiondiagnostic for major pharma in helping to identify patients that will benefitfrom a particular drug and then monitoring the drug’s effectiveness. ANGLE has establishedformal collaborations with world-class cancer centers and is working with thesecancer centers to demonstrate key applications for its Parsortix non-invasivecancer diagnostic system as a liquid biopsy. In addition to cancer cells, theParsortix technology has the potential for deployment for other clinicallysignificant cell types in the future.                            

ANGLE’s Parsortixsystem is available for research use worldwide and is CE-IVDD Marked forindicated clinical use in Europe. The Company’s first clinical application isin ovarian cancer.