Date: Tuesday, June 14, 2016
Session Time: 4:30pm-6:00pm
Presentation Time: 4:30pm-4:42pm
Location: Room 310
In patients, allograft survival requires a cocktail of immunosuppressive drugs, while experimentally antibodies targeting the innate immune system have been shown to induce long-term tolerance, with severe side effects. We here induced long-term tolerance by nanomedicine delivery of rapamycin to myeloid cells.
We developed a hybrid nanoparticle encapsulating rapamycin (R-HDL), which has inherent affinity for innate immune cells. In a mouse allogeneic heart transplantation model, we applied this nanotherapy using a regimen involving 3 intravenous tail vein injections of 5 mg/Kg rapamycin during the first week. Using a combination of radiolabeling, in vivo PET-CT imaging and flow cytometry, we evaluated allograft and cellular specificity. Subsequently, the innate immune system's response and allograft survival were extensively monitored.
R-HDL nanoparticles, ~30 nm in diameter, had a high rapamycin encapsulation efficiency of ~65%. Radiolabeled R-HDL was observed to specifically accumulate in the transplanted heart and to be mainly associated with myeloid cells.
We showed in the transplanted heart, a significant reduction of Ly-6Chi / Ly-6Clow as well as CD25– / CD25+ cells. Most excitingly, our nanomedicine treatment resulted in a dramatic enhancement of allograft survival.
We here presented a novel nanomedicine treatment paradigm to redirect rapamycin to innate immune cells and induce long-term allograft survival.
CITATION INFORMATION: Braza M, Lameijer M, Perez-Medina C, Reiner T, Nahrendorf M, Fayad Z, Duivenvoorden R, Ochando J, Mulder W. Rapamycin Nanotherapy Delays Heart Transplant Rejection. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:Braza M, Lameijer M, Perez-Medina C, Reiner T, Nahrendorf M, Fayad Z, Duivenvoorden R, Ochando J, Mulder W. Rapamycin Nanotherapy Delays Heart Transplant Rejection. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/rapamycin-nanotherapy-delays-heart-transplant-rejection/. Accessed February 25, 2021.
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