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Terasaki Talks: Dr. Reza Abdi

Abstract:

The targeted delivery of therapeutic drugs to lymph nodes (LNs) provides an unprecedented opportunity to improve the outcomes of transplantation and immune-mediated diseases. The high endothelial venule is a specialized segment of LN vasculature that uniquely expresses peripheral node addressin (PNAd) molecules. PNAd is recognized by MECA79 mAb. We previously generated a MECA79 mAb–coated microparticle (MP) that carries tacrolimus. Although this MP trafficked to LNs, it demonstrated limited therapeutic efficacy in our transplant model. Here, we have synthesized a nanoparticle (NP) as a carrier of anti-CD3 and optimized the conjugation strategy to coat the NP surface with MECA79 mAb (MECA79-anti-CD3-NP) to enhance LN accumulation. As compared with nonconjugated NPs, a significantly higher quantity of MECA79-NPs accumulated in the draining lymph node (DLN). Many MECA79-NPs underwent internalization by T cells and dendritic cells within the LNs. Short-term treatment of murine cardiac allograft recipients with MECA79-anti-CD3-NP resulted in significantly prolonged allograft survival in comparison with the control groups. Prolonged graft survival following treatment with MECA79-anti-CD3-NP was characterized by a significant increase in intragraft and DLN Treg populations. Treg depletion abrogated the prolongation of heart allograft survival. We believe this targeted approach of drug delivery could redefine the methods of administering immune therapeutics in transplantation.

Biography:

Dr. Abdi is a Transplant Nephrologist at Brigham and Women’s Hospital. His research theme focuses on studying the mechanisms of immune regulation of allo- and auto- immune responses with the ultimate goal of devising novel immunomodulatory strategies. He is also deeply committed to training the next generation of physician scientists in transplantation research.

Event Information

Event Date 07-01-2020 8:00 am
Event End Date 07-01-2020 9:00 am
Registration Start Date 06-21-2020
Cut off date 07-01-2020 8:15 am
We are no longer accepting registration for this event

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