Grant: Operating Grant: Industry-partnered Collaborative Research

Recent revolution in anti-cancer therapy utilizes the antibody's power to target cancer cells with chemotoxins. This approach of conjugating toxin to antibody (ADC= antibody drug conjugates) with specific affinity to cancer cells have dramatically improved both the safety and efficacy of the treatment. The most notable recent success is Kadcyla which combines DM1 toxin with anti-HER2 antibody to treat breast cancer. A critical factor in developing a successful ADC is an antibody's ability to internalize itself once it binds to the target cancer cell's biomarkers (receptors). However, many cancer cell specific receptors do not internalize efficiently enough to advance into clinical development. iProgen has developed a peptide domain that can be engineered into an antibody and dramatically boost the antibody's internalization efficiency on target cancer cell. When applied to existing ADCs, we saw a dramatic boost in efficacy and safety of the ADC drugs. These were all done on cancer cell lines in-vitro model. Now, we are testing these candidates in conventional cell line xenograft models. While such cancer cell line models have merits for cancer research, the cell lines used do not adequately predict efficacy of anticancer drugs in the clinic. Drs. Wang at the Living Tumor Lab (www.livingtumorlab.com) has established next-generation patient-derived cancer models, which more closely resemble a patient's cancer than the existing standard cancer models. Such models provide valuable tools for further testing our drug candidates. We want to see whether the ADC improvement in efficacy seen on cell line can translate into in improvement in efficacy and or safety in the respective animal model testing. We are also interested in testing new ADC targets that have either failed to advance in clinic or that have largely been ignored by the pharmaceutical industry largely due to the poor internalization property of the antibody-receptor complex.