Skip to main content
. 2022 May 30;21(9):655–675. doi: 10.1038/s41573-022-00476-6

Fig. 5. Strategies to overcome immune rejection for allogeneic cell therapy.

Fig. 5

Schematic representation of current approaches being investigated to overcome immune mechanisms that underlie the rejection of transplanted allogeneic cells. (1) Systemic immunosuppression is the only clinically approved approach, but it results in compromised immunity and risk of malignancy. Several drug regimens and combinations of approaches including treatments with rapamycin and/or glucocorticoids, cyclosporine A and/or cyclophosphamide, cytokine blockade and/or JAK–STAT inhibitors, and B cell depletion with antibodies, are available to enable cell and organ transplantation. (2) Cell encapsulation using biocompatible polymers provides a physical barrier that limits cell–cell contact required for activation and functional lysis by T cells and natural killer (NK) cells. (3) Tolerance induction through direct overexpression of ligands for inhibitory pathways in transplanted cells leads to induction of tolerance. (4) Hypoimmunogenic cells (that is, ‘universal’ stem cells) generated through CRISPR-mediated deletion of major histocompatibility complex (MHC) molecules and overexpression of CD47 limit T and NK cell-mediated cell killing and limit macrophage-mediated phagocytosis. ADCC, antibody-dependent cell-mediated cytotoxicity; FC, fragment crystallizable region; IFN, interferon; MAC, membrane attack complex; MHC, major histocompatibility complex; TCR, T cell receptor.