Improving Efficacy of RNase Cancer Therapy by Pharmacokinetics

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DESCRIPTION (provided by applicant): 6. Project Summary Abstract The goal of this project is to develop a safe yet potent drug utilizing an EVade(tm) Ribonuclease. The EVade(tm) Ribonucleases are recombinant variants of mammalian enzymes that are effective in mouse xenograft models of multiple cancer types without exhibiting significant toxicity. While they are effective, Quintessence is interested in increasing the potency of the EVade(tm) Ribonucleases to improve clinical outcome. Many of the FDA approved cancer therapies work by very similar mechanisms, including genotoxicity, anti-metabolite and microtubule binding. Newer, targeted therapies are being developed, with a few of these drugs already on the market. We believe an agent with a novel mechanism of action and mild side effect profile, such as an EVade(tm) Ribonuclease, is a strong candidate for cancer therapy. We will change the pharmacokinetic profile of the EVade(tm) Ribonucleases. The EVade(tm) RNase and macromolecules for conjugation were selected because they have shown efficacy in vivo. The initial experiments will produce and characterize the next generation EVade(tm) RNases while the second round will determine the in vivo effects of combining the conjugated EVade(tm) Ribonucleases at various concentrations. The ultimate goal of this project is to develop a new safe AND effective tool for physicians to treat patients with cancer.