The Potential to Immunocloak Renal Allografts

DESCRIPTION provided by applicant The focus of this project is a novel immunomodifying therapy that provides protection from early allograft rejection in the absence of the standard toxic systemic immunosuppressive drug regimens This novel therapy is a nano barrier membrane called NB LVF consisting of a matrix made of laminin vitrogen fibronectin and type IV collagen NB LVF is applied to andquot immunocloakandquot the luminal surfaces within the renal vasculature by covering the point of contact between donor vascular endothelial cells and the host immune system without adversely affecting renal function The result is an apical surface that is non thrombogenic and non immunogenic and significantly delays the onset of rejection fold over untreated controls by preventing allo recognition that normally occurs immediately upon reperfusion A warm acellular Exsanguinous Metabolic Support EMS perfusion technology that is entering clinical trials is the platform used to apply NB LVF The immunocloaking technology will be a follow on product that can be applied to a kidney allograft during ex vivo EMS perfusion If the results of our studies support our hypotheses and prove that the immunogenicity of renal allografts can be further reduced by trapping passenger leukocytes that migrate into the recirculating EMS perfusate to prevent reentry into the kidney the use of a concordant low dose immunosuppressive drug monotherapy potentiates long term graft survival the mechanisms of protection provided by NB LVF are fully elucidated along with an understanding of how it degrades over time along the vasculature and a strategy for the organ specific re application of NB LVF posttransplant to replace systemic drug regimens can be achieved the NB LVF technology will mark a new era in transplantation It is envisioned that the ability to eliminate toxic systemic immunosuppressive drug regimens will lead to a paradigm shift where instead of daily immunosuppressive drug regimens it will become feasible to re administer NB LVF every three to four weeks However even if these goals are not fully achieved NB LVF will still be clinically relevant The ability to use NB LVF treatment to eliminate systemic immunosuppression during the early posttransplant period will be important to expanding the cadaveric kidney donor pool with warm ischemically damaged DCD kidneys The acute tubule necrosis that is the result of ischemic damage leads to delayed graft function that in turn is associated with the risk of developing currently untreatable chronic rejection By eliminating the need for systemic immunosuppressive drugs that are in of themselves nephrotoxic during the early posttransplant period of acute tubule necrosis the severity and duration of delayed graft function would be ameliorated The consultants and collaborators involved in this project are internationally recognized experts in their respective field and their involvement in this project will significantly increase the likelihood of successfu outcomes PUBLIC HEALTH RELEVANCE The goal of this project is use new technology referred to as andquot immunocloakingandquot to eliminate the need for the toxic chronic systemic immunosuppressive drug regimens that are the standard of care today We have developed a product referred to as the NB LVF nano barrier membrane that can be applied pre transplantation in an organ specific manner to immunocloak the interface between the donor graft vasculature and the recipientandapos s immune system The goal of this project is to develop the ability to reapply NB LVF post transplantation where instead of daily multi drug regimens NB LVF will be administered intravascularly once a month