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Potentiating the Cytotoxic Effects of Immunotoxins

Immunotoxins are genetically engineered proteins fusing antibodies with plant or microbial toxins.  Such proteins can be used in the treatment of cancers by selecting antibodies against cancer specific antigens and appropriate toxins.  A particular immunotoxin can vary in its pharmacokinetic properties based on the choice of antibody and toxin.  One important hurdle in the path of an effective toxin is access to the cytoplasm.  Following internalization, the toxin must escape the endosome before it is degraded by proteolytic enzymes or the increasingly acidic environment.  This project strives to enhance the intracellular delivery of immunotoxins via specialized polymers or peptide sequences as well as model the delivery pathway to help identify important points for improvement.