Genetic engineering to block immune destruction of transplanted cells succeeds in macaques.
A major challenge in the development of cell therapies is how to stop a patient’s immune response from killing transplanted cells derived from an unmatched donor. Various approaches to address this problem are under investigation, but a particularly elegant solution would be to create ‘universal’ donor cells that could be transplanted into any recipient without being rejected. In a study in Nature Biotechnology, Schrepfer and colleagues1 describe an exciting step toward this goal in a non-human primate model. Using donor cells with three genetic modifications — deletion of human leukocyte antigen (HLA) class I and II molecules and overexpression of CD47 — the authors demonstrate sustained immune evasion by human and macaque induced pluripotent stem cells (iPSCs) in immunocompetent rhesus macaques. This work is important because it is likely to pave the way to cell therapies that avoid immune rejection without the need for immunosuppression.
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Fig. 1: Cellular engineering to generate hypoimmune cells.
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Authors and Affiliations
Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Asuncion Borrero Borrego & Saar Gill
Salamanca Biomedical Institute (IBSAL), University of Salamanca, Salamanca, Spain
Asuncion Borrero Borrego
Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, Philadelphia, PA, USA
Saar Gill
Cellular Therapy and Transplantation, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA
Saar Gill
Corresponding author
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The authors declare no competing interests.
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Borrero Borrego, A., Gill, S. Hypoimmune cells resist rejection in monkeys.
Nat Biotechnol (2023). https://doi.org/10.1038/s41587-023-02013-1
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Published: 23 October 2023
DOI: https://doi.org/10.1038/s41587-023-02013-1
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