SHORT DESCRIPTION A PEG-PPS nanoparticle technology for targeted delivery of roxadustat to myeloid cells to promote transplantation tolerance.
NU Tech ID: NU 2023-184
IP STATUS
PCT Application pending (PCT/US2024/055220)
DEVELOPMENT STAGE
TRL-5 - Prototype Validated in Relevant Environment: Preclinical testing in mouse models validated immunomodulatory potential.
BACKGROUND Heart and other solid-organ transplants are life-saving for patients with advanced organ failure, but long-term outcomes are limited by immune rejection of the foreign tissue. Strategies for treating this issue rely on broad immunosuppressants, but standard regimens (calcineurin inhibitors, antiproliferative agents, steroids, and mTOR inhibitors) are linked to serious complications, including infections, kidney damage, malignancies, metabolic disease, and accelerated graft vessel disease. There is a clear unmet need for new solutions that can preserve graft acceptance while reducing the long-term harms and practical burden of chronic immunosuppression. An attractive alternative is to target just the immune cells involved in organ rejection. Such a targeted approach would suppress activity locally around the transplant, without broad immunosuppressive effects, increasing likelihood of transplant acceptance, while decreasing side effects of therapies. Myeloid cells represent a particularly attractive target for these therapies.
ABSTRACT Northwestern researchers developed a targeted nanoparticle platform that enhances transplant tolerance by increasing the activity of a protein called HIF‑2α in myeloid cells. The core product is a spherical micelle nanocarrier made from a PEG‑b‑PPS block copolymer that encapsulates a HIF‑2α‑inducing agent such as roxadustat, and is designed to specifically targets myeloid cells (i.e. monocytes and macrophages). In a murine heart transplant models using co-stimulatory blockade, the inventors show that this approach boosted HIF‑2α and CSF1R expression and promoted the development of tolerogenic macrophages, reduced damaging T‑cell responses, supported regulatory T cells, and improved cardiac allograft survival with less vessel damage and fewer donor‑specific antibodies while reducing some systemic effects of free roxadustat such as high erythropoietin levels. This technology represents a novel and more selective strategy for long‑term graft protection.
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KEYWORDS Nanoparticles, roxadustat, transplantation tolerance, macrophage-targeting, immunomodulation, HIF stabilization, heart transplant, PEG-PPS, nanoparticle delivery, tolerogenic macrophages