Dendritic cell membrane-coated nanoparticles protect allogeneic transplanted cells and tissues

The efficacy of allogeneic cell and tissue transplantation has substantially increased to provide therapies for tissues lost to disease or trauma. However, sustained alloantigen recognition can lead to chronic rejection and thus most patients receive long-term immune suppression, which has associated risks. Herein, we develop an alloantigen-specific therapy that is based on modifying nanoparticles with cell membranes from donor cells, with the intent to limit immune activation to the alloantigens present in the membrane. Membranes were obtained from dendritic cells as they express major and minor antigens associated with rejection. The membrane-coated nanoparticles (MCNPs) had alloantigens on the surface as detected by flow cytometry, and in vitro co-culture with T cells led to proliferation. MCNPs are trafficked to professional antigen presenting cells in vivo, differently than the uncoated NPs alone, and can induce proliferation of T cells through indirect, but not direct, antigen presentation. MCNP administration significantly improved engraftment, without immunosuppression, of a skin transplant with a minor major histocompatibility mismatch. Furthermore, MCNP treatment protected allogeneic islets from rejection in a minor and major antigen mismatch model. Collectively, MCNPs represent an antigen specific platform for sustaining the survival of transplanted cells or tissues without sustained immune suppression.