Signaling Protein Based Test
The foundational protein for Beacon's laboratory developed test is called teratocarcinoma derived growth factor-1, aka Cripto-1, and was licensed from the National Institutes of Health and National Cancer Institute for exclusive use by Beacon to develop and commercialize laboratory developed tests and test kits for early cancer recognition, detection, screening and monitoring purposes. Cripto-1 is a required protein for tumor formation, progression and invasion, and has been detected in 50-100% of carcinomas of the breast, colon, lung, pancreas, gallbladder, stomach, endometrium and cervix.
Laboratory Developed Test
BeScreened™-CRC is an ELISA-based multiplexed, CLIA laboratory developed colorectal cancer (CRC) screening test. The test used three blood-based tumor-associated protein biomarkers; a patented oncoprotein called teratocarcinoma derived growth factor-1 (TDGF-1, Cripto-1); carcinoembryonic antigen (CEA), a well-established biomarker associated with CRC; and an extracellular matrix protein involved in early stage tumor stroma changes. These three proteins are intimately involved in the structure, function, and regulation of activities associated with CRC tumorigenesis; generation, invasion, progression and migration.
BeScreened-CRC was developed exclusively by Beacon Biomedical, Inc. Beacon is certified under CLIA to perform high complexity clinical laboratory testing and is providing BeScreened-CRC to the public as alternate test option for CRC screening test to those individuals who are unwilling or unable to use existing recommended fecal-based screening test or imaging procedures. This test’s performance characteristics has been established by Beacon Biomedical in a cross-sectional study in patients of both genders, 50 years of age or older, and who are at typical average-risk for colorectal cancer.
The assay results are processed through Beacon’s proprietary relational algorithm and evaluated against the algorithm’s healthy patient-state status criteria. Patients that fall within the acceptance criteria are reported as negative for the likely presence of CRC with a recommendation to stay compliant with their individual healthcare and screening needs. Patients calculated as outliers to that same criteria are reported as positive with an elevated-risk of CRC’s presence with a recommendation to follow-up with their physician to schedule a screening colonoscopy.
As a laboratory developed test (LDT) under the Centers for Medicare and Medicaid Services’ (CMS’) Clinical Laboratory Improvement Amendments (CLIA), BeScreened-CRC is approved for clinical use and it does not require FDA clearance or approval.
Published Literature — Abbreviated List
Caterina Bianco, Luigi Strizzi, Mario Mancino, Aasia Rehman, Shin Hamada, Kazuhide Watanabe, Antonella De Luca, Brenda Jones, Gabriela Balogh, Jose Russo, Daniel Mailo, Raffaele Palaia, Giuseppe D’Aiuto, Gerardo Botti, Francesco Perrone, David S. Salomon and Nicola Normanno, Identification of Cripto-1 as a Novel Serologic Marker for Breast and Colon Cancer
Nadia Pereira Castro, Maria Cristina Rangel, Tadahiro Nagaoka, Hideaki Karasawa, David S. Salomon and Caterina Bianco,Cripto-1: At the Crossroads of Embryonic Stem Cells and Cancer
Caterina Bianco, Maria Cristina Rangel,Nadia P. Castro, Tadahiro Nagaoka,Kelly Rollman, Monica Gonzales,and David S. Salomon, Role of Cripto-1 in Stem Cell Maintenance and Malignant Progression
Caterina Bianco, Luigi Strizzi, Mario Mancino, Kazuhide Wantanabe, Monica Gonzales, Shin Hamada, David S. Salomon, et al, Regulation of Cripto-1 Signaling and Biological Activity by Caveolin-1 in Mammary Epithelial Cells
Kazhuhide Wantanabe, Shin Hamada, Caterina Bianco, Mario Mancino, Tadahiro Nagaoka, Monica Gonzales, Luigi Strizzi, David S. Salomon,Mechanism of Signal Transduction: Requirement of Glycosylphosphatidylinositol Anchor of Cripto-1 for trans Activity as a Nodal Co-receptor
Cripto-1 Intellectual Property
Licensed Cripto-1 Patents, NIH License Number L-282-2014/0
U.S. Patent No. 7,078,176
PCT Application No. PCT/US02/02225
U.S. Provisional Patent Application No. 60/264,643
Canadian Patent No. 2,434,694
Australian Patent No. 2002236871
Europe Patent No. 1370869 (Validated in Germany, France, Italy, Spain, Ireland, Great Britain, Switzerland)
Japan Patent No. 3821779
Radisky D, Muschler J, Bissell MJ. Order and Disorder: The Role of Extracellular Matrix in Epithelial Cancer. Cancer investigation. 2002;20(1):139-153.
Rissell MJ, Hall HG, Parry G. How Does Extracellular Matrix Direct Gene Expression? J Theor Biol. 1982;99(1):31–68
Howe A, Aplin AE, Alahari SK, Juliano RL. Integrin Signaling and Cell Growth Control. Curr Opin Cell Biol. 1998;10(2):220–231.
De Archangelis A, Georges-Labouesse E. Integrin and ECM Functions: Roles in Vertebrate Development. Trends Genet. 2000;16(9):389–395.
Streuli C. Extracellular Matrix Remodeling and Cellular Differentiation. Curr Opin Cell Biol. 1999;11(5):634–640.
Jones FS, Jones PL. The Tenascin Family of ECM Glycoproteins: Structure, Function, and Regulation During Embryonic Development and Tissue Remodeling. Dev Dyn. 2000;218(2):235–259.
Su B-B, Shi H, Wan J.Role of serum carcinoembryonic antigen in thedetection of colorectal cancer before and after surgical resection. World Journal of Gastroenterology : WJG. 2012;18(17):2121-2126. doi:10.3748/wjg.v18.i17.2121.
Locker GY, Hamilton S, Harris J, Jessup JM, Kemeny N, Macdonald JS, Somerfield MR, Hayes DF, Bast RC. ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. J Clin Oncol. 2006;24:5313–5327. [PubMed]
Duffy MJ, van Dalen A, Haglund C, Hansson L, Holinski-Feder E, Klapdor R, Lamerz R, Peltomaki P, Sturgeon C, Topolcan O. Tumour markers in colorectal cancer: European Group on Tumour Markers (EGTM) guidelines for clinical use. Eur J Cancer. 2007;43:1348–1360.
Gold P, Freedman SO. Demonstration of tumor-specific antigens in human colonic carcinomata by immunological tolerance and absorption techniques. J Exp Med. 1965;121:439–462
Pignatelli M, Durbin H, Bodmer WF.Carcinoembryonic antigen functions as an accessory adhesion molecule mediating colon epithelial cell-collagen interactions. Proc Natl Acad Sci USA. 1990;87:1541–1545.