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.
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.
