Potential to Immunocloak Renal Allografts

描述(由申请人提供)：本提案正在重新提交，以供高级NIAID技术SBIR计划(PA-06-134)考虑，该计划提供为期两年的第一阶段资金，最高可达300,000美元/年。根据我们评审员的建议，我们修改了该提案，以解决围绕一种新技术的主要临床问题，该新技术提供了一种可以在移植前以特定器官的方式应用的非系统治疗方法。这项技术包括一种生物工程屏障，它被聚合成三维透明膜。屏障膜通过覆盖血管内皮细胞和宿主免疫系统之间的接触点，用来免疫覆盖血管腔内的管腔表面。其结果是形成了一种生物工程的心尖表面，它不会导致血栓和免疫原性。在缺乏全身免疫抑制药物的情况下，生物工程屏障膜在小鼠皮肤和犬肾脏模型上都显示出显著延迟急性同种异体移植排斥反应的发生的能力，大约是未经处理的对照组的5倍。了解屏障膜在体内的保留以及其潜在的保护机制(S)将有助于开发有一天可能导致提高移植物存活率的治疗策略，而不需要传统的慢性全身免疫抑制。及早证明人体同种异体移植的有效性将对产品开发产生积极影响，因为它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：这项提案正在重新提交给NIAID先进技术计划，并在我们的总结声明中进行了建议的修订。为了解决与慢性全身免疫抑制相关的问题，我们开发了一种产品，可以在移植前以特定于器官的方式应用，以“免疫遮盖”移植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移植的有效性，确定免疫遮盖涉及的保护机制，并提供对肾血管内屏障膜在体内保留的了解。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.