BREAKTHROUGH RESEARCHUSING THE PARSORTIX SYSTEM DISCOVERS ROLE OF BODY'S OWN IMMUNE SUPPRESSOR CELLSIN PROMOTING CANCER METASTASIS
Research using Parsortixdiscovers large CTC clusters of 10-30 cells comprising both cancer cells andimmune suppressor cells, which dramatically increase cancer metastasis
Parsortix system offerskey capabilities for research into CTC clusters to target new ways to disablethe cancer-promoting role of immune suppressor cells
GUILDFORD, SURREY / ACCESSWIRE / April 26, 2019 / ANGLE plc (AIM:AGL OTCQX:ANPCY), a world-leading liquid biopsy company, is delighted to announce that its ParsortixTM system has been utilised in further groundbreaking new cancer research which demonstrates for the first time the role of myeloid-derived suppressor cells (MDSCs) as part of large circulating tumor cell (CTC) clusters, which are 50x more likely to generate metastasis than single CTCs.
The research, led by Professor Dario Marchetti at the Biomarker Research Program, Houston Methodist Research Institute (Houston, Texas, United States) in conjunction with the Center for Precision Health, University of Texas and MD Anderson Cancer Center has been published as a peer-reviewed publication in the International Journal of Molecular Sciences.
The research investigated metastatic breast and melanoma cancers and found that the Parsortix system harvested large CTC clusters comprising 10-30 cells in 100% of the patient samples (n=33). In contrast, a leading antibody CTC system was unable to capture large CTC clusters in any samples and only identified small CTC clusters comprising 2-3 cells in less than 50% of the samples.
The research work investigated for the first time the role of MDSCs in CTC clusters. MDSCs are a subset of the body's immune cells, which are distinct from neutrophils which have been separately studied by other ANGLE customers, and provide the body with a sophisticated mechanism to balance an extensive immune response to protect from excessive tissue damage and autoimmune disorders. MDSCs interact with other immune cell types including T cells, dendritic cells, macrophages and natural killer cells to regulate their functions. Unfortunately cancer cells can take an advantage of those immunosuppressive mechanisms to protect themselves against the body's anti-cancer immune responses.
Investigation of the role of MDSCs in CTC clusters is seminal work because, instead of assisting the patient's immune system to combat the cancer, the MDSCs actually play a number of key roles in promoting cancer metastasis by:
• suppressing the body's immune response to the cancer
• enhancing CTC survival and proliferation
• increasing CTC metastatic potency and dissemination.
The research work investigated each of these factors. A key finding was that, when CTCs were cultured, the addition of MDSCs lead to an increase in the number of CTCs by a factor of 10 compared to a control CTC culture without the addition.
The development of metastasis, the spread of cancer to distant sites primarily via the blood, is responsible for more than 90% of all cancer-related deaths. If metastasis could be suppressed by disrupting the role of the MDSCs in the CTC clusters then patient outcomes could be dramatically improved.
ANGLE's Parsortix system has again been shown to have key advantages in harvesting CTC clusters, expanding the potential use of the Parsortix system in the growing CTC cluster research field with the prospect of routine use as a companion diagnostic for immunotherapy and other drugs to disrupt CTC clusters.
Professor Dario Marchetti at the Biomarker Research Program,Houston Methodist Research Institute, Houston, Texas, United States, commented:
"This study is the first to demonstrate the detection and functionality of naïve, heterotypic clusters consisting of CTCs and circulatory MDSCs directly isolated from the peripheral blood of metastatic cancer patients. This opens up a whole new area of research with the prospect of stabilizing cancer progression to reduce its spread or metastasis. The Parsortix state-of-the-art technology platform played a key role in enabling us to directly capture/isolate heterotypic CTC clusters from patients' blood for downstream interrogation."
ANGLE Founder and Chief Executive, Andrew Newland, commented:
"Investigation into CTC clusters and their impact on metastasis, an area where ANGLE's Parsortix system is strongly differentiated, is beginning to take off with further seminal work by another one of ANGLE's leading customers. This work identifies the role of immune suppressor cells within the CTC cluster highlighting key new areas for drug development with the potential for Parsortix to be routinely used as a companion diagnostic. Our ultimate aim is for the Parsortix system to be routinely used for all cancer patients in the future."
ANGLE is a world leading liquid biopsy company with sample-to-answer solutions. ANGLE's proven patent protected platforms include an epitope-independent circulating tumor cell (CTC) harvesting technology and a downstream analysis system for cost effective, highly multiplexed analysis of nucleic acids and proteins.
ANGLE's cell separation technology is called the ParsortixTM system, and it enables a liquid biopsy (a simple blood test) to be used to provide the cells of interest to the user in a format suitable for multiple downstream subsequent analyses. CTCs enable the complete picture of a cancer to be seen as they allow DNA, RNA and protein analysis and the live cells harvested can be cultured. The Parsortix technology is the subject of 21 granted patents in Europe, the United States, Canada, India, China, Japan and Australia with three extensive families of patents are being progressed worldwide. The system is based on a microfluidic device that captures cells based on a combination of their size and compressibility. The Parsortix system has a CE Mark in Europe for the indicated use and FDA clearance is in process for the United States with a 400 subject study in metastatic breast cancer. ANGLE is seeking to be the first ever FDA cleared CTC harvesting system and only the third ever FDA cleared liquid biopsy test. ANGLE has already undertaken two separate 200 subject clinical studies under a program designed to develop an ovarian cancer pelvic mass triage test, with the results showing best in class accuracy (ROC-AUC) of 95.1%. The pelvic mass triage assay has undergone further refinement and optimisation, and is currently in the process of a clinical verification study.
ANGLE's technology for the multiplex evaluation of proteins and nucleic acids of all types is called the HyCEADTM Ziplex® platform and is based on a patented flow through array technology. It provides for low cost, highly multiplexed, rapid and sensitive capture of targets from a wide variety of sample types. A proprietary chemistry approach (the HyCEAD method) allows for the capture and amplification of over 100 biomarkers simultaneously in a single reaction. The HyCEAD Ziplex system is ideal for measuring gene expression and other markers directly from Parsortix harvests and was used in the ovarian cancer pelvic mass triage test to achieve best in class accuracy (ROC-AUC) of 95.1%.
ANGLE's proprietary technologies can be combined to provide automated, sample-to-answer results in both centralised laboratory and point-of-use cartridge formats.
ANGLE has established formal collaborations with world-class cancer centres and major corporates such as QIAGEN, Abbott and Philips, and works closely with leading CTC translational research customers. These Key Opinion Leaders (KOLs) are working to identify applications with medical utility (clear benefit to patients), and to secure clinical data that demonstrates that utility in patient studies. The body of evidence as to the benefits of the Parsortix system is growing rapidly from our own clinical studies in metastatic breast cancer and ovarian cancer and also from KOLs with 20 peer-reviewed publications and numerous publicly available posters, available on our website.
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