Development of antibody-drug conjugates that use actin-targeting warheads

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Cancer metastasis involves the spread of cancer cells from one organ to another and is thecause of 90% of cancer-related deaths. Current therapies fail to block metastasis effectively,and our invention of novel actin-targeted ADCs will address this unmet need. Dynamicmodifications of the actin cytoskeleton are essential for cancer cells to breakthrough tissueand blood vessel barriers during metastasis. Targeting this "actin addiction" is the goal of thisproject, which is built on our detailed knowledge of potent natural inhibitors of actin. Ourmultidisciplinary team has designed, synthesized and tested novel actin toxin analogs thatblock growth, motility and invasion of metastatic cancer cells in vitro. Currently, we are linkingthese to antibodies used in oncology, and will test these novel ADCs in preclinical mousemodels of metastatic cancers relevant to each clinically used antibody. These studies willmeasure effects of our ADCs on tumour progression and metastasis.