SBIR-STTR Award

The aim of this project is to produce monoclonal antibody-drug conjugates with therapeutic potency for the selective destruction of human cancer cells. Antibody-drug conjugates prepared by current approaches do not achieve high levels of free drug inside targeted cells. We will replace the current moderately cytotoxic anti-cancer drugs with maytansinoids which are 100 to 1000 fold more cytotoxic. The maytansinoids will be linked via disulfide bonds, which are stable in circulation, but cleaved intracellularly. Tle maytansinoids will be synthetically modified to incorporate disulfide or thiol groups. The most cytotoxic of these drugs will be conjugated to monoclonal antibodies by disulfide bonds and assessed for in vitro cytotoxicity to cancer cells. In vivo pharmacokinetic properties will be evaluated in mice.Awardee's statement of the potential commercial applications of the research:The ultimate goal is to create new therapeutic agents with high selectivity and low systemic toxicity for the treatment of cancer. Currently, there are no major competitive products in the field because antibody-drug conjugates tested so far have been therapeutically ineffective. We seek to develop new technology to resolve the problems that have made current approaches for the targeted delivery of drugs for cancer unsuccessful. The program aims to open the door to clinical use of antibody-drug conjugates of highly cytotoxic drugs.National Cancer Institute (NCI)

There is no text on file for this abstract.Thesaurus termsantineoplastic, colorectal neoplasm, drug design /synthesis /production, drug screening /evaluation, immunoconjugate, maytansine, monoclonal antibody, neoplasm /cancer chemotherapy, neoplasm /cancer immunotherapy, nonhuman therapy evaluation multidrug resistance SCID mouse, immunofluorescence techniqueNational Cancer Institute (NCI)