Targeting Donor Immune Cells for the Promotion of Immune Regulation After Vascularized Composite Tissue Transplants
Abstract
Anti-rejection medications are associated with significant complications post-transplant, including higher rate of infection and cancer. In addition, all face and extremity transplant recipients develop rejection despite the use of available anti-rejection drugs. Therefore, better understanding how the transplanted face or extremity triggers rejection and the development of novel therapies that minimize rejection and prevent systemic effects of anti-rejection medications are of paramount importance. The current research proposal has two main objectives: (1) Investigate the exact immune cells present in the transplanted organ that trigger rejection. (2) Develop a novel therapy to prevent rejection that involves treatment of the transplanted organ prior to transplantation, promoting immune regulation and minimizing any systemic side effects related to high-doses of anti-rejection medications. This proposal is innovative for three main reasons: (1) We will use animal and human experimental approaches to answer our questions in combination with advanced technological tools such as live imaging of immune cells. (2) We have identified a unique drug capable of "educating" the donor immune cells prior to transplantation, permitting the development of a new concept of rejection prevention that lacks systemic toxicity to the recipient. (3) For the past 6 years, we have been collecting samples from patients that had undergone face/extremity transplants in our center, which will allow us to correlate our animal findings with the more relevant observations in humans. To our knowledge, this is the largest collection of face/extremity transplant samples in the world and a precious resource that we wish to utilize to help improve care of current and future face/extremity transplant recipients. This proposal addresses three main Focus Areas of this award: (1) Immunomodulation approaches and mechanisms. (2) Exploiting inflammatory processes, controlling and modulating a patient s immune response to improve existing therapies and maximize outcomes. (3) Understanding mechanisms of immune rejection. The results of this study will allow us to better understand the rejection process by specifically characterizing subsets of donor immune cells present in the transplant organ and to apply a novel therapeutic strategy that targets the transplanted organ instead of the whole body. This approach could be applied to future face/extremity transplants for regulating the immune response and minimizing systemic toxicity of anti-rejection medications.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610689
Entities
People
- Leonardo V Riella
Organizations
- United States Army