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Engineering Antibodies for Improved Targeting of Solid Tumors

Antibody therapeutics have great potential for improving cancer treatment efficacy and limiting healthy cell toxicity by directing cytotoxic effectors specifically to the tumor tissue.  Unfortunately, attempts to treat solid tumors with these approaches have been limited by an inability of the targeting molecules to completely saturate the tumor tissue, leaving regions of cancer cells untargeted and viable.  Mathematical modeling of the relevant transport processes identifies several factors that influence antibody distribution in tumors including antibody dose, affinity, molecular size, antigen concentration, target turnover, vascular permeability, and tumor physiology.  We are using a combination of mathematical modeling, protein engineering, and in vitro and in vivo experiment to optimize these parameters to develop improved targeting agents.