Antibody venom conjugates

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Antibody Drug Conjugates (ADCs) are an emerging class of drugs that combines antibody and drug payload. The antibody targets the drug payload to specific targeted cells improving both safety and efficacy. To date that are 8 FDA approved ADC drugs all for oncology application using small molecule drugs. Although these ADCs with small molecules encompasses superior efficacy and safety than non-targeted small molecule drugs, it is increasingly evident that they succumb to the same multi-drug resistance by the cancer cells. In this project, we are exploring the synthesis and evaluation of larger molecule cyclical peptide toxin drugs that cancer cells will not be able to develop resistance to. This proposal merges unique chemical training outcomes in the Perrin lab on bioconjugation of novel venom-derived peptides to antibodies with an industrial partnership with iProgen, an emerging biopharmaceutical company in Vancouver. With a short time-frame, we have identified a qualified postdoctoral fellow who has experience in peptides and is prepared to engage in this project.Traditionally, these cyclic peptide toxins are rarely used for oncology application due to a variety of systemic toxicity; however, by utilizing an ADC platform, we hypothesize that this new class of toxins may represent an important and untapped class of anti-cancer drug payloads to be unlocked. The Perrin lab has extensive experience in the synthesis and evaluation of cyclic and bicyclic peptides including the synthesis of both phalloidins and amanitins, which showcase know-how in this domain and as toxins represent back-up molecules as we advance new toxic scaffolds as payloads for ADCs. Outcomes will be first-in-class compositions of chemically conjugated toxins to antibodies that will be validated in vitro by our industrial partner, iProgen.