Hypoimmune islets achieve insulin independence after allogeneic transplantation in a fully immunocompetent non-human primate
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Allogeneic transplantation of pancreatic islets for patients with difficult-to-control diabetes mellitus is severely hampered by the requirement for continuous immunosuppression and its associated morbidity. We report that allogeneic transplantation of genetically engineered (B2M−/−, CIITA−/−, CD47+), primary, hypoimmune, pseudo-islets (p-islets) results in their engraftment into a fully immunocompetent, diabetic non-human primate wherein they provide stable endocrine function and enable insulin independence without inducing any detectable immune response in the absence of immunosuppression. Hypoimmune primary p-islets may provide a curative cell therapy for type 1 diabetes mellitus.
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Sana Biotechnology reported the 1-month data on the first person treated with donor-derived islets that have been made deficient in β2-microglobulin and the class II transactivator molecule to reduce major histocompatibility complex class II and overexpression of CD47 to decrease attack by natural killer cells, using a protocol previously reported in primates.
“Sana Biotechnology (Seattle, WA, USA) reported the 1month data on the first person treated with donorderived islets that have been made deficient in β2microglobulin and the class II transactivator molecule to reduce major histocompatibility complex class II and overexpression of CD47 to decrease attack by natural killer cells, using a protocol previously reported in primates.76”
From The future of type 1 diabetes therapy (2025) · cites this paper as [76]
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- Authors
- Hu, X., White, K., Young, C., Olroyd, A. G., Kievit, P., Connolly, A. J., Deuse, T., & Schrepfer, S.
- Affiliations
- Sana Biotechnology (United States) (US)
- Corresponding author
- Schrepfer, Sonja
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2024-03
- Volume
- 31
- Issue
- 3
- Pages
- 334-340.e5
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W4391643843
- Cited by
- 73
- References
- 31
- Citations by year
- 2026: 29 · 2025: 31 · 2024: 13
- FWCI
- 30.83
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Oregon National Primate Research Center
- University of California, San Francisco (PCT/US2022/074878)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
- Keywords
- type 1 diabetes, insulin independence, nonhuman primate model, B2M knockout, CD47, immune tolerance, islet engraftment, cell therapy
- MeSH terms
- Animals, Diabetes Mellitus, Type 1, Humans, Insulin, Islets of Langerhans, Primates, Transplantation, Homologous, Islets of Langerhans Transplantation
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