Potential to Immunocloak Renal Allografts

免疫斗篷同种异体肾移植的潜力

• 批准号: 7748049
• 负责人: Lauren Brasile
• 金额: $ 20万
• 依托单位: BREONICS, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-25 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7748049
• 关键词: Acute; Address; Adverse effects; Affect; Alabama; Allografting; Antibodies; Apical; Attention; Biomedical Engineering; Blood; Blood Vessels; Canis familiaris; Cardiac Death; Chronic; Clinical; Clinical Trials; Collagen Type IV; Data; Dependence; Development; Development Plans; Diffusion; Evaluation; Event; Fibronectins; Foundations; Funding; Future; Glycosaminoglycans; Goals; Graft Rejection; Graft Survival; Human; Immune; Immune response; Immune system; Immunologic Tests; Immunosuppression; Immunosuppressive Agents; Kidney; Laminin; Lead; Malignant Neoplasms; Mediating; Membrane; Modeling; Monitor; Mus; NID gene; National Institute of Allergy and Infectious Disease; Nutrient; Opportunistic Infections; Organ; Organ Donor; Oxygen; Pharmaceutical Preparations; Phase; Phase I Clinical Trials; Proteoglycan; Recommendation; Renal function; Research; Risk; Screening procedure; Skin; Small Business Innovation Research Grant; Surface; Technology; Tissue Grafts; Transplantation; Treatment Efficacy; Universities; Vascular Endothelial Cell; Vascular Endothelium; cell motility; commercialization; design; immune function; immunogenic; in vivo; innovative technologies; kidney allograft; new technology; prevent; product development; programs; public health relevance; receptor; response; technology development; treatment strategy

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.

描述（由申请人提供）：该提案已由高级NIAID Technology SBIR计划（PA-06-134）重新提交，以供资金考虑，该计划可提供2年的最高300,000美元的1阶段资金。遵循审稿人的建议，我们修订了该提案，以解决围绕一种新技术的主要临床问题，该技术提供了一种非系统性治疗方法，该治疗方法可以以特定于器官的方式应用。该技术由一个生物工程屏障组成，该障碍物聚合成三维透明膜。通过覆盖血管内皮和宿主免疫系统之间的接触点，将屏障膜应用于血管空间内的腔表面。结果是一个非血统和非免疫原性的生化顶端表面。在没有全身免疫抑制药物的情况下，生物工程的屏障膜已经证明了使用鼠皮肤和犬肾模型在未经处理的对照组上显着延迟急性同种异体移植排斥的发作约5倍。了解屏障膜的体内保留率，同时了解其潜在的保护机制将有助于制定治疗策略，这些策略有一天可能会导致移植物的生存增强，而无需传统的慢性系统性免疫抑制。早期证明人类同种异体移植的功效将对产品开发产生积极影响，因为能够进行临床试验，从而导致更快的商业化途径。公共卫生相关性：通过我们的摘要声明中的建议修订，该提案已重新提交到NIAID先进技术计划。为了解决与慢性全身免疫抑制相关的问题，我们开发了一种可以以器官特异性方式进行预植入的产品，以“免疫”移植组织与宿主免疫系统之间的界面。该项目将确定与人肾脏同种异体移植物一起使用的疗法的功效，确定与免疫产生有关的保护机制，并提供对肾血管内屏障膜的体内保留的理解。该项目的目的是制定治疗策略，这些策略有一天可能导致同种异体移植的生存，而无需传统的慢性全身免疫抑制。