Breast Cancer Collaboration

RNS Number : 1072S

Angle PLC

19 September 2014

 

For immediate release

19 September 2014

ANGLE plc ("the Company")

BREAST CANCER COLLABORATION WITH THE UNIVERSITY OF SOUTHERN CALIFORNIA NORRIS COMPREHENSIVE CANCER CENTER

ANGLE plc (AIM: AGL), the specialist medtech company, is pleased to announce it has signed a collaboration agreement with the University of Southern California (USC) Norris Comprehensive Cancer Center to investigate the clinical use of the Parsortix system for breast cancer. 

The USC Norris Comprehensive Cancer Center (USC Norris) is a world leader in cancer research and is designated by the National Cancer Institute as one of the nation's leading comprehensive cancer centers.

The research collaboration will be led by Dr Julie E. Lang, M.D., F.A.C.S., Associate Professor of Surgery, specialising in breast cancer and notably in molecular profiling of circulating tumor cells in breast cancer, inflammatory breast cancer and radiation induced-sarcoma. Dr Lang is involved with clinical trials and translational studies focused on finding better treatments for breast cancer patients via a multidisciplinary and personalised approach.

Metastasis is responsible for virtually all breast cancer related deaths.  American Society for Clinical Oncology guidelines now call for the biopsy of metastatic sites (the secondary cancer locations) for biomarker testing to guide decision making for systemic therapy.  These metastatic biopsies are invasive, often requiring surgery, and therefore can cause the patient considerable additional complications.  Furthermore, such metastatic biopsies can be expensive and may delay aspects of the patient's ongoing treatment. 

The metastatic biopsy yields no medical benefit other than a better understanding of the status of the disease to aid therapeutic decisions, such as the most appropriate chemotherapy regime.  Dr Lang and her team have investigated over several years the possibility of securing the same or similar information from circulating tumour cells (CTCs) obtained from the patient's blood through a simple blood test.  In pursuing this area of research, USC Norris has used the existing in-market CTC system along with several other systems under development, before developing its own in-house process.  However all of these systems have had specific drawbacks that have limited their applicability.

Over the last four months, the team at USC Norris has evaluated the performance of ANGLE's Parsortix system and have now decided to focus their efforts on using the Parsortix system to harvest CTCs for analysis.  As a result of its previous work, the team has already developed core processes needed to undertake RNA analysis of the breast cancer CTCs once harvested by the Parsortix system.

The aims for the collaboration with USC Norris in breast cancer are to:

·     Evaluate if CTCs may be successfully isolated and profiled from Stage IV breast cancer patients, with or without background subtraction of contaminating leukocytes

·     Determine if CTCs may serve as a surrogate for biopsies of macrometastases by paired comparisons (CTC and metastases) for each patient

·     Study if profiling CTCs' biology sequentially over time may explain treatment resistance to HER2 directed therapy, chemotherapy, or endocrine therapy, and further identify novel treatment targets.

ANGLE is strongly focused on establishing the use of the Parsortix system in clinical practice.  To achieve this, the top priority is the establishment of collaborations with key opinion leaders at world class research centres.  These key opinion leaders are working to identify applications with medical utility (clear benefit to patients), and to secure clinical data that demonstrate that utility in patient studies.  ANGLE believes this is the optimal approach for unlocking the multi-billion dollar worldwide market available to the Company and its potential strategic partners.  

ANGLE Founder and Chief Executive, Andrew Newland, commented:

"Extending our key opinion leader collaborations in the United States is a key objective.  Dr Lang and her team are world leaders in CTC analysis for breast cancer.  Metastatic breast cancer patients are subjected to a battery of invasive tests, and the outcome remains poor.  We hope that, using the Parsortix system to harvest CTCs, Dr Lang and her team may be able to develop new approaches which replace invasive biopsies of secondary cancers with non-invasive blood tests and improve the overall outcome for breast cancer patients in the future."

For further information:

ANGLE plc	01483 685830
Andrew Newland, Chief Executive Ian Griffiths, Finance Director
Cenkos Securities Stephen Keys, Dr Christopher Golden (Nominated adviser) Andy Roberts, Christian Hobart (Sales)	020 7397 8900
Buchanan Mark Court, Fiona Henson, Sophie Cowles	020 7466 5000

ABOUT USC NORRIS COMPREHENSIVE CANCER CENTER

USC Norris Comprehensive Cancer Center has been leading the fight to make cancer a disease of the past. As one of the eight original comprehensive cancer centers in the United States, its mission is to treat and prevent cancer by advancing and integrating education, research, and personalized patient care. For 40 years, USC Norris has been revolutionizing cancer research with innovative surgical techniques and novel cancer treatments. The cancer center's breakthroughs and discoveries in the field of epigenetics have led the way to a greater understanding of the underlying causes of cancer and new methods of prevention, detection, and treatment. With a multidisciplinary team of more than 250 dedicated scientists and physicians, USC Norris Comprehensive Cancer Center offers patients hope in the battle against cancer.  Dr Julie Lang's research group will receive funding support from ANGLE.

Explanation of Frequently Used Terms in connection with the Parsortix system

Term	Explanation
Biopsy	Process by which cancer cells are removed from the tumour for molecular analysis
Capture	Process for capturing target cells from sample
Capture efficiency	Proportion of target cells captured
CD45	The CD45 antibody recognises the human CD45 antigen, also known as the leukocyte common antigen.  WBC are CD45+ whereas CTCs are CD45-.  Staining with CD45 often used as a negative confirmation that CTCs are not WBC
Cell-free DNA	Genomic DNA found in the plasma
Cell labelling	Technique involving the staining of target cells with fluorescent and/or chromogenic markers for cell identification
Cell lines	Cultured cells
CE Mark	Regulatory authorisation for the sale of products for clinical use in the European Union
Circulating tumour cell	Cancer cell that is circulating in the patient blood
CTC	Circulating tumour cell
CTC labelling	CTCs are often labelled with three markers and are formally identified as CTCs if they are CK+, CD45-, DAPI+
CK	Cytokeratin
CK+	A cell positive for the presence of cytokeratin protein or mRNA with the presence of distinct cytokeratins often used to identify epithelial cells
Clinical application	Use in treating patients
Clinical samples	Patient samples usually blood
Clinical use	Use in treating patients
Cultured cells	Cultured cells grown in the laboratory from human-derived cells used for experimental work
Cytokeratin	Cytokeratins are family of intracytoplasmic cytoskeleton proteins with members  showing tissue specific expression
DAPI	A nuclear stain that is often used to identify the nucleus in a cell.
DEPArray™	A commercial single cell isolation system
DNA	Deoxyribonucleic acid (DNA) the molecule that encodes the genetic instructions used in the development and functioning of all known living organisms and many viruses
Downstream technologies	Technologies used to undertake molecular analysis of harvested cells after the separation has taken place
EGFR	The epidermal growth factor receptor a signalling molecule which is typically present on the cell surface and can cell activity including cell proliferation. Mutations in EGFR or deregulation have been associated with a number of cancers including ~30% of all epithelial cancers
Enrichment	Generic term for concentrating target cells or molecules in a starting heterogeneous mixture
EpCAM	The EpCAM protein is found spanning the membrane that surrounds epithelial cells, where it is involved in cell adhesion
EpCAM+ cells	Cells that express EpCAM.  CTCs can be either EpCAM+ or EpCAM-
Epithelial cells	Cells that line the surfaces and cavities of the body
Epithelial CTCs	CTCs that are epithelial often based on EpCAM+
Epithelial-mesenchymal transition	Process by which epithelial cells lose their cell polarity and cell-cell adhesion, and gain migratory and invasive properties to become mesenchymal cells. EMT is thought to occur as part of the initiation of metastasis and is often responsible for cancer progression
EMT	Epithelial-mesenchymal transition
FDA	U.S. Food and Drug Administration responsible for authorised medical products in the United States
FDA 510(k)	A 510(k) is a premarket submission made to FDA to demonstrate that the device to be marketed is at least as safe and effective, that is, substantially equivalent, to a legally marketed device that is not subject to Premarket Approval. Submitters must compare their device to one or more similar legally marketed devices and make and support their substantial equivalency claims
Genome	Genetic material of an organism. The genome includes both protein coding and non-coding sequences
Harvest	Process for recovering captured cells from the separation system to allow molecular analysis
Harvest efficiency	Proportion of target cells harvested
Harvest purity	The number of target cells (such as CTCs) in the harvest as a proportion of the WBC. The minimum purity from which downstream analysis is possible is 0.5%.  Analysis of one target cell therefore requires no more than 200 WBC be in the harvest
HER2	A member of the epidermal growth factor receptor (EGFR/ERBB) family. Amplification or overexpression of HER2 has been shown to play an important role in the development and progression of certain aggressive types of breast cancer. In recent years the protein has become an important biomarker and target of therapy for ~30% of breast cancer patients
HNV	Healthy normal volunteer
HT29	Cultured colorectal cancer cell line
In-cassette labelling or in-situ labelling	CTC labelling for cell identification undertaken inside the separation system
KRAS	A signalling molecule frequently mutated in the development of many cancers
Leukocytes	White blood cells
Liquid biopsy	Term used for the process of obtaining cancer cells (or cell-free DNA) from a blood sample.  Unlike solid biopsy, liquid biopsy is non-invasive and repeatable.
Mesenchymal CTCs	CTCs generally lacking epithelial markers with mesenchymal features
Metastasis	Spread of a cancer from one site to another
Molecular analysis	Analysis of DNA, RNA and protein often used to determine the mutational status of a patient
mRNA	Messenger RNA used to direct the synthesis of proteins
NSCLC	Non Small Cell Lung Cancer
Off-chip labelling	CTC labelling for cell identification of harvested cells undertaken outside the separation system
Paired samples	Two related samples often used to compare different systems
Personalised cancer care	Treating a patient individually based on their personal data often including mutational and disease status
Plasma	Pale-yellow liquid component of blood obtained following removal of cells
Pre-labelled cell lines	Cells which are labelled often with a fluorescent label to facilitate identification during analysis or enrichment
RNA	Ribonucleic acid performs multiple vital roles in the coding, decoding, regulation, and expression of genes. Together with DNA, RNA comprises the nucleic acids, which, along with proteins, constitute the three major macromolecules essential for all known forms of life
Separation	Term used for processing of a sample through the Parsortix system
Single cell analysis	Extraction of a single target cell from the harvest for analysis
Solid biopsy	Standard process for surgically excising (cutting out) cells from a solid tumour when that tumour is accessible.
Spiked cell experiments	Experiments where cultured cells are added (spiked) to HNV blood to assess the capture and harvest efficiency of the system
WBC	White blood cells
WGA	Whole genome amplification
Whole genome amplification	Method for amplification of an entire genome necessary for the picogram amounts of genomic DNA present in a single cell

 

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