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SELECTBIO Conferences Current Trends in Antibody Drug Conjugates


Bioanalytical & Pre-Clinical Development Strategies for ADCs

Sanghamitra Bhattacharjee, Senior Scientist, Theramyt Novobiologics Pvt. Ltd

The concept of a “magic bullet” in immune oncology has been a dream for centuries. Recent technological advances enabled antibody-drug conjugates to materialize that dream. Approvals of Brentuximab-vedotin and Trastuzumab-emtansine reveal the potential for antibody-drug conjugates to offer newer therapeutic avenues for cancer patients. These antibody drug conjugates (ADCs) are expected to be superior over either monoclonal antibodies or cytotoxic small molecules.  More than thirty ADCs are under clinical development. We will talk about development of trastuzumab-emtansine as a case study. Product development strategies for ADCs in general involve selection of an antibody, a cytotoxic drug, chemical conjugation, linker technology and effective drug release. Preclinical development includes rodent and primate studies to decipher two prime aspects that are efficacy and toxicity. Efficacy studies include pharmacokinetics and pharmacodynamics profiling. Toxicity indices consist of histopathology, neurologic, ophthalmic examinations and effect of repeat dosing. Bioanalytical studies include ADC serum ELISA, total antibody serum ELISA, emtansine plasma LC-MS/MS and immunogenicity testing. In 2008, Lewis Phillips and colleagues published their study that elucidates bio analytical and preclinical development of trastuzumab-emtansine. They demonstrated target specific cytotoxicity in trastuzumab resistant HER2 overexpressing tumors with increased linker stability and improved safety profile in rodents. In 2014, Diana et al. demonstrated that trastuzumab-emtansine is nearly three times more effective than trastuzumab alone in inhibiting cell proliferation in vitro while both the drugs showed comparable levels of ADCC in Her2 overexpressing cell lines. In vivo

Add to Calendar ▼2015-03-02 00:00:002015-03-03 00:00:00Europe/LondonCurrent Trends in Antibody Drug ConjugatesCurrent Trends in Antibody Drug Conjugates in Bangalore, IndiaBangalore,