Apr 21, 2016
Urothelial Carcinoma (UCC, also known as transitional cell carcinoma) is a cancer that starts in the urothelial cells, which line the inside of the bladder and other parts of the urinary tract. According to the American Cancer Society there were over 76,000 new cases of bladder cancer diagnosed and over 15,000 deaths from advanced bladder cancer in the United States in 2014. At stage I, the 5-year survival rate is about 88% but at stage IV, the 5-year survival rate falls to 15%. Poor prognosis and ineffective therapies for patients with advanced bladder cancer make the discovery of new drugs very important for the treatment of this common disease.
In a pioneering study published last month in Molecular Cancer Therapeutics, researchers at Agensys Inc. identified the SLITRK6 protein as a new UCC biomarker and developed a novel antibody-drug conjugate (ADC) targeting SLITRK6 for the treatment of metastatic bladder cancer. Recent advances in the antibody-drug conjugate (ADC) technology and two recently approved ADCs have brought this drug class to the forefront of drug development in oncology.
Extensive immunohistochemistry (IHC) analysis using BioGenex high throughput IHC Staining system (i6000), BioGenex Super Sensitive Polymer-HRP IHC Detection System and BioGenex IHC reagents, showed that SLITRK6, a member of the SLITRK family of type I transmembrane proteins, is expressed in multiple epithelial tumors including bladder, lung and breast cancer as well as in glioblastoma. Examination of 509 formalin fixed paraffin embedded (FFPE) biopsies, representing all stages of bladder cancer showed that SLITRK6 is expressed in 90% of Urothelial Carcinomas, 100% of Metastatic bladder cancers, and 54% of other bladder cancers. The normal tissue expression profile of SLITRK6 was examined using tissue microarrays (TMAs) containing 37 different human tissues including those recommended in the FDA normal tissue panel.
To create the antibody-drug conjugate (ADC) - a panel of fully human monoclonal antibodies specific for SLITRK6 was conjugated to the highly toxic antimitotic agent Monomethyl auristatin E (MMAE). MMAE is a drug so toxic that it can only be used as a conjugate, and works by preventing mitotic division thus suppressing tumor growth. The novel ADCs showed potent in vitro and in vivo cytotoxic activity. The most potent ADC, ASG-15ME, is currently in Phase I Clinical Trials for the treatment of metastatic urothelial cancer.
To read the Research Manuscript Click here.
BioGenex designs, develops, and commercializes advanced fully-automated molecular pathology systems for cancer diagnosis, prognosis, personalized medicine, and life science research. The recent introduction of our eFISHency integrated workflow solution for FISH laboratories and miRNA system for characterization of CUP and for undifferentiated tumors is a game changer that has no rival in the industry. Our fully-automated molecular pathology workstations are the most advanced system globally. Our customer focused approach, with premier after sales support and excellent technical service, provides the best in class customer care. Our spirit of innovation drives us to deliver cutting edge technology, years ahead of our competition, and the finest systems for life Science research and diagnostics.
By Stephanie Erhard, April 20, 2016