Sana Biotechnology publishes HIP-modified pancreatic islet cells data

Sana Biotechnology announced that Cell Stem Cell has published a paper titled “Hypoimmune islets achieve insulin independence after allogeneic transplantation in a fully immunocompetent non-human primate.” The paper evaluated a transplant of Sana‘s engineered allogeneic, hypoimmune, or HIP-modified pancreatic islet cells into a fully immunocompetent, diabetic non-human primate, or NHP. These modified islet cells, which cluster into effective endocrine organoids, are termed “pseudo islet grafts”. The results demonstrated that the HIP-modified p-islets engrafted following intramuscular injection and provided stable endocrine function, enabling insulin independence in the absence of immunosuppression. The transplant setting was purposely designed to be a high immunological bar by maximizing the donor-to-recipient mismatch. Diabetes mellitus was chemically induced in the recipient as shown by the development of major blood glucose instability and the need for daily insulin injections to control blood sugar. Following stabilization of glucose with insulin treatment, the diabetic NHP underwent transplantation of the HIP p-islets without any induction or maintenance immunosuppression and the administration of insulin was tapered to zero over the course of nine days. Rapidly following HIP p-islet transplantation, the diabetic NHP recipient showed tightly controlled blood glucose levels, was completely insulin-independent, continuously healthy, and exhibited no physical or behavioral abnormalities for the six-month study duration. C-peptide levels, which are a marker for endogenous insulin production and release, reached the normal levels observed prior to induction of diabetes. Furthermore, there was no indication that the allogeneic HIP p-islet graft induced any immune recognition or any type of immune response at any time. To demonstrate that there was no regeneration or recovery of an endogenous islet cell population in the diabetic NHP, HIP p-islets were eliminated using an anti-CD47 antibody. The antibody blocked the protective CD47 signal and triggered a “missing self” innate immune cell response that led to the rapid destruction of the HIP p-islet graft. Following the anti-CD47 treatment, blood glucose levels in the diabetic NHP began to fluctuate and increase markedly, and insulin injections needed to be resumed. It was thus demonstrated that the tightly controlled blood glucose levels and insulin independence was entirely due to well-functioning HIP p-islets.