Potential to Immunocloak Renal Allografts

描述（由申请人提供）：该提案正在重新提交给高级NIAID技术SBIR计划（PA-06-134）进行资金考虑，该计划提供为期2年的第一阶段资金，每年高达30万美元。根据审稿人的建议，我们修改了提案，以解决围绕新技术的主要临床问题，该技术可提供非系统性治疗，可以器官特异性方式应用于移植前。该技术由生物工程屏障组成，该屏障被聚合成三维透明膜。通过覆盖血管内皮和宿主免疫系统之间的接触点，屏障膜被应用于“免疫斗篷”血管空间内的管腔表面。其结果是一个生物工程的根尖表面，是非血栓性和非免疫原性。在缺乏全身免疫抑制药物的情况下，在小鼠皮肤和犬肾脏模型中，生物工程屏障膜已被证明能够显著延缓急性同种异体移植排斥反应的发生，大约是未治疗对照的5倍。了解屏障膜的体内保留及其潜在的保护机制将有助于制定治疗策略，有朝一日可以提高移植物的存活率，而不需要传统的慢性全身免疫抑制。人类同种异体移植的早期疗效证明将对产品开发产生积极影响，因为有能力更早地进行临床试验，从而更快地实现商业化。公共卫生相关性：该提案正在重新提交给NIAID先进技术计划，并在我们的摘要声明中建议进行修订。为了解决与慢性全身性免疫抑制相关的问题，我们开发了一种产品，可以在移植前以器官特异性的方式应用于移植物组织和宿主免疫系统之间的界面。该项目将确定该疗法用于人类同种异体肾脏移植的有效性，确定涉及免疫遮蔽的保护机制，并提供对肾脏血管内屏障膜在体内保留的理解。该项目的目标是开发治疗策略，有朝一日可以提高同种异体移植物的存活率，而不需要传统的慢性全身免疫抑制。

DESCRIPTION (provided by applicant): This proposal is being resubmitted for funding consideration by the Advanced NIAID Technology SBIR Program (PA-06-134) that provides Phase 1 funding of up to $300,000/year for up to 2-years. Following the recommendations of our reviewers we have revised the proposal to address the major clinical questions surrounding a new technology that provides a non-systemic treatment that can be applied pre-transplantation in an organ-specific manner. The technology consists of a bioengineered barrier that is polymerized into a tri-dimensional transparent membrane. The barrier membrane is applied to "immunocloak" the luminal surfaces within the vascular spaces by covering the point of contact between vascular endothelium and the host immune system. The result is a bioengineered apical surface that is non-thrombogenic and non-immunogenic. In the absence of systemic immunosuppressive drugs, the bioengineered barrier membrane has demonstrated the ability to significantly delay the onset of acute allograft rejection approximately 5-fold over untreated controls using both murine skin and canine kidney models. An understanding of the in vivo retention of the barrier membrane along with understanding its underlying protective mechanism(s) will help to develop treatment strategies that could one day lead to enhanced graft survival without the traditional need for chronic systemic immunosuppression. Early demonstration of efficacy for human allografts will have a positive impact on product development by having the ability to perform clinical trials earlier resulting in a faster path to commercialization. PUBLIC HEALTH RELEVANCE: This proposal is being resubmitted to the NIAID Advanced Technology Program with the recommended revisions in our Summary Statement. To address the problems associated with chronic systemic immunosuppression, we have developed a product that can be applied pre-transplantation in an organ-specific manner to "immunocloak" the interface between the graft tissue and the host immune system. This project will establish efficacy of the therapy for use with human renal allografts, determine the protective mechanisms involved in immunocloaking and provide an understanding of the in vivo retention of the barrier membrane within the renal vasculature. The goal of this project is to develop treatment strategies that could one day lead to enhanced allograft survival without the traditional need for chronic systemic immunosuppression.