Antonio Vitale
Design, prototype development and testing of an antibody-drug conjugate using a novel colchicine derivative.
Rel. Jacek Adam Tuszynski. Politecnico di Torino, Corso di laurea magistrale in Ingegneria Biomedica, 2020
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Abstract
From the Paul Ehrlich’s idea of the “magic bullet”, developed more than 100 years ago, outstanding findings pushed many researchers and companies to getting into the ADCs technology. The modular structure of the ADCs based on three major constituents, a monoclonal antibody (mAb), a linker molecule and a cytotoxic payload, theoretically allows the appropriate efficacy and controlled therapeutic toxicity for the treatment of many cancers and not only. Nowadays, many other diseases are also treated with this strategy. Today, seven ADCs are marketed and several hundred are advancing through different preclinical and clinical stages of development. The purpose of this Master’s thesis work was to design, synthetize and test in-vitro an novel antibody-drug conjugate (ADC) using Panitumumab as a biological molecule and a new produced colchicine derivative named CCI-001 as a payload.
First, several reactions have been carried out in order to obtain the chemical conjugation between the CCI-001 with a heterobifunctional pegylated linker, taking advantages of two different strategies
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