News Flash: Goodwin Biotechnology and Transporin Announce a Technology Collaboration that Enhances the Ability of Antibody Drug Conjugates to Target and Deliver Payloads into Diseased Cells (click here for press release)
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The radioisotope image is provided as a courtesy from Ekaterina (Kate) Dadachova, PhD and Arturo Casadevall, MD, PhD as published in Einstein’s dynamic duo of the decade. Einstein. 2010; Summer / Fall: 38-45.
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MBD-Peptide Technology Enhances ADC Targeting and Intracellular Delivery of the PayloadModern medicine has made significant strides in a number of disease conditions; however, there remain a number of diseases where advancements are needed to improve the detection, monitoring and treatment of these conditions. In a variety of cancers, for example, conventional chemotherapy has limited specificity for the diseased cells. Therefore, high doses of systemic chemotherapy are used with limited success and the patients experience significant side effects. Monoclonal Antibodies (mAbs) conjugated with a payload such as a drug or radioisotope are showing some promise based on their ability to target diseased cells; however, a significant amount of the conjugate is lost because a high percentage of the mAb conjugate does not reach the target. Based on the complexity of the antibody:linker:payload conjugate, premature cleavage of the payload from the conjugate, inability of the conjugate to breach the cell wall, binding to non-target sites and / or getting eliminated from the body prematurely, some suggest that greater than 95% of the administered dose will never reach the intracellular target.1,2 Therefore, higher drug doses are needed, which increases the cost of therapy and the side effect profile. However, the possibility of improving the selectivity of therapy for a number of diseases can be enhanced by the use of targeting agents. A number of cancers (breast, prostate, colon, ovarian, pancreatic, gastric, lung, etc.), chronic conditions (arthritis, osteoporosis, atherosclerosis and other cardiovascular diseases), autoimmune diseases, and other maladies are now increasingly being viewed as secondary to chronic inflammatory conditions. As such, they are under stress. The condition of cellular stress can be any type of stress such as thermal, immunological, cytokine, oxidative, metabolic, anoxic, endoplasmic reticulum, protein unfolding, nutritional, chemical, mechanical, osmotic and glycemic. Diseased cells under stress are targeted by the metal-binding domain (MBD) of human insulin-like growth factor binding protein-3 (IGFBP-3). A short peptide from IGFBP-3 (MBD peptide) confers intracellular targeting to “stressed” cells, as well as to cancer cells — which typically up-regulate cellular stress-coping 2-11 mechanisms. Transporin, Inc. protects MBD peptides with a comprehensive portfolio of issued patents in the U.S. and worldwide (US Pat. Nos. 8,536,135; 7,662,624; 7,618,816; 7,611,893; 7,371,813; 6,914,049; 6,887,851; 6,861,406). Further, the IGFBP-3 protein (which includes the MBD sequence in its natural context) is a component of an FDA-approved product (iPlex® [mecasermin rinfabate]). In addition, there are over a dozen studies in animal models and one drug candidate — Nephrilin™ in late stage preclinical testing for neuro-inflammatory stress — that utilizes the MBD. 2-7 Method of Action
Applications/Opportunities
The resultant MBD-peptide agent can be used for diagnostic purposes, for monitoring diseases and / or as a therapeutic modality.
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