John Garner

300th article! Mal-PEG-PLGA and mPEG-PLGA from PolySciTech used in development of immune-targeting nanoparticles to reduce organ rejection

Blog Post created by John Garner on Oct 10, 2018

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Organ transplantation is a life-saving surgical technique in which the organs or tissues from a donor can be placed into a recipient to replace damaged or missing organs. Organ rejection occurs when the recipient’s immune system recognizes the transplanted organs or tissue as ‘non-self’ and launches an immune response against them. Recently researchers at Johns Hopkins University School of Medicine, Harvard Medical School, Tufts University, Universite de Lille (France), Hamad bin Khalifa University (Qatar), and University of Maryland used mPEG-PLGA (AK102) and Mal-PEG-PLGA (A110) from PolySciTech (www.polyscitech.com)  to develop targeted nanoparticles to prevent immune-rejection of the transplanted tissue. This technology holds promise to prevent the potentially fatal incidence of tissue rejection. Furthermore, this article officially marks the 300th publication citing PolySciTech as the source of their research products since the first article published in 2011. Read more: Bahmani, Baharak, Mayuko Uehara, Liwei Jiang, Farideh Ordikhani, Naima Banouni, Takaharu Ichimura, Zhabiz Solhjou et al. "Targeted delivery of immune therapeutics to lymph nodes prolongs cardiac allograft survival." The Journal of clinical investigation 128, no. 11 (2018). https://www.jci.org/articles/view/120923

  “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.”

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