Potential to Immunocloak Renal Allografts

描述（由申请人提供）：该提案正在重新提交高级NIAID技术SBIR计划（PA-06-134）的资金考虑，该计划提供为期2年的第一阶段资金，每年高达30万美元。根据我们的评审员的建议，我们修改了提案，以解决围绕一项新技术的主要临床问题，该技术提供了一种非全身性治疗，可以以器官特异性方式在移植前应用。该技术由生物工程屏障组成，该屏障聚合成三维透明膜。屏障膜通过覆盖血管内皮和宿主免疫系统之间的接触点来“免疫封闭”血管空间内的管腔表面。结果是生物工程化的顶端表面是非血栓形成和非免疫原性的。在不存在全身免疫抑制药物的情况下，使用小鼠皮肤和犬肾模型，生物工程屏障膜已经证明能够显著延迟急性同种异体移植物排斥反应的发生，约为未处理对照的5倍。了解屏障膜的体内滞留沿着了解其潜在的保护机制将有助于开发治疗策略，该策略有朝一日可能导致增强的移植物存活，而无需传统的慢性全身免疫抑制。早期证明人体同种异体移植物的有效性将对产品开发产生积极影响，因为能够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：该提案将重新提交给NIAID先进技术计划，并在我们的总结声明中提出了建议的修订。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，该产品可以以器官特异性方式在移植前应用，以“免疫封闭”移植组织和宿主免疫系统之间的界面。该项目将确定用于人肾移植物的治疗的有效性，确定免疫封闭中涉及的保护机制，并提供对肾血管系统内屏障膜的体内保留的理解。该项目的目标是开发治疗策略，有一天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.