Regulatory T-Cell Expansion and Immune Modulation in Vascularized Composite Tissue Transplants
Abstract
Anti-rejection medications are associated with significant complications post-transplant, including higher rate of infection, cancer, and kidney disease. In addition, all face and extremity transplant recipients develop rejection despite the use of available anti-rejection drugs. Therefore, 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 a very promising molecule that slows down the rejection process by promoting the immune system own regulatory army. 2. Assess whether our molecule will reduce the risk of infection and cancer compared to current 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 limb transplantation models, humanized skin transplant model, and genetic expression of the transplanted organs. 2. We have developed a unique drug capable of selectively increasing the most well-defined immune regulatory cell that is responsible for the prevention autoimmunity and rejection of the transplanted organ. 3. Our new treatment approach would permit minimization of global immunosuppression and its related systemic toxicity to the transplant recipient, while still allowing the immune system to fight an infection or a cancer. This proposal addresses the main Focus Areas of this Award: 1. Develop novel approaches for improving VCA immune tolerance. 2. Identify unique immunosuppression requirements for VCA compared to other solid organ transplants. The results of this study will allow us to apply a novel and better anti-rejection molecule, thereby decreasing the complications associated with the current medications. This approach could be applied to future extremity/face transplants for regulating the immune response and minimizing systemic toxicity of anti-rejection medications.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110904
Entities
People
- Leonardo V Riella
Organizations
- Massachusetts General Hospital
- United States Army