Translational research case studies:Development of antibodies for cancer diagnosis and therapy

Antibodies are primary tools in several areas of biomedical sciences,including basic research,diagnostics,and molecular therapeutics.Antibodies are widely used in diagnostic applications for clinical medicine.Analysis of cells and tissues in pathology laboratories includes the use of antibodies on tissue sections.Further,antibodies are making rapid inroads into medical therapeutics,driven by technological evolution from chimeric and humanized to fully human antibodies.The therapeutic antibody market has the potential to reach $30 billion by 2010.Our lab has developed a monoclonal antibody,named Met4 that was raised against the extracellular domain of Met specifically with the goal of measuring Met in FFPE tissues.The Met receptor kinase is expressed on the cell surface of a significant number and variety of human primary solid tumors and in their metastases.The characterization of the Met4 antibody suggests it should possess adequate performance for quantification of Met expression in clinical specimens.We have also generated a fully human Fab fragment against EGFR;conjugated it to taxol as an immuno-chemotherapy agent;and investigated its in vitro anti-tumor efficacy on EGFR positive A431 epidermoid carcinoma cells.The Fab-Taxol conjugate inhibited A431 cell proliferation at low concentrations and in a dose-responsive manner;furthermore,almost 100% of cells underwent apoptosis after treatment with Fab-Taxol.Our findings suggest that this Fab-Taxol conjugate could be a potential immuno-chemotherapeutic drug for clinical treatment of EGFR over-expressing tumors.