Improving Efficacy of RNase Cancer Therapy by Pharmacokinetics

描述（由申请人提供）：6。项目概要摘要本项目的目标是利用EVade（TM）核糖核酸酶开发一种安全而有效的药物。EVade（tm）核糖核酸酶是哺乳动物酶的重组变体，其在多种癌症类型的小鼠异种移植模型中有效，而不表现出显著的毒性。虽然它们是有效的，但Quintessence对提高EVade（TM）核糖核酸酶的效力以改善临床结果感兴趣。许多FDA批准的癌症疗法通过非常相似的机制起作用，包括遗传毒性、抗代谢物和微管结合。更新的靶向治疗正在开发中，其中一些药物已经上市。我们相信，具有新的作用机制和轻微副作用的药物，如EVade（TM）核糖核酸酶，是癌症治疗的有力候选药物。我们将改变EVade（tm）核糖核酸酶的药代动力学特征。选择EVade（tm）RNase和大分子用于缀合，因为它们在体内显示出功效。最初的实验将产生并表征下一代EVade（tm）RNA酶，而第二轮将确定结合的EVade（tm）核糖核酸酶在各种浓度下的体内作用。该项目的最终目标是为医生开发一种新的安全有效的工具来治疗癌症患者。

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.