Vatuximab(Trademark): Optimizing Therapeutic Strategies for Prostate Cancer Based on Dynamic MR Tumor Oximetry

Abstract

Abstract : Targeting the vasculature of tumors promises a new effective therapy for prostate cancer. We propose a new approach targeting the blood vessels in the tumor. Specifically, a novel antibody 3G4, which targets phosphatidylserine (PS) expressed on tumor vasculature was developed by Thorpe et al. and is being developed by Peregrine Pharmaceuticals for clinical trials. Normally, PS exclusively resides on the cytosolic leaflet of the plasma membrane. However, in tumors PS becomes externalized and provides a viable target. The agent not only targets various tumors, but also induces vascular damage and tumor regression with minimal accompanying toxicity. In developing a new therapy, critical issues include scheduling, optimal combination with other interventions to achieve synergy and early assessment of efficacy. Magnetic resonance imaging allows us to follow the induction and development of tumor vascular damage providing new insight into spatial and temporal activity and facilitating effective combination with the hypoxic cell selective cytotoxin tirapazamine. Importantly, this therapy may be effective at any stage of tumor development, and could be most effective for advanced disease. Success will confirm the potential of this new therapeutic approach to prostate cancer in man and lay the foundation for future clinical trials.