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 the**cause 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. Dynamic**modifications of the actin cytoskeleton are essential for cancer cells to breakthrough tissue**and blood vessel barriers during metastasis. Targeting this "actin addiction" is the goal of this**project, which is built on our detailed knowledge of potent natural inhibitors of actin. Our**multidisciplinary team has designed, synthesized and tested novel actin toxin analogs that**block growth, motility and invasion of metastatic cancer cells in vitro. Currently, we are linking**these to antibodies used in oncology, and will test these novel ADCs in preclinical mouse**models of metastatic cancers relevant to each clinically used antibody. These studies will**measure effects of our ADCs on tumour progression and metastasis.