Sana Biotechnology Presents Data at ISSCR 2022 Annual Meeting Showing Survival of Transplanted Hypoimmune iPSC-Derived Differentiated Cell Types Without Immunosuppression in Non-Human Primates
First demonstration of the survival of allogeneic islet cells, cardiomyocytes, and retinal pigment epithelium cells transplanted into an immunocompetent non-human primate model without any immune suppression
The islet autoimmune data suggest that cells with hypoimmune (HIP) edits evade allogeneic immune response and autoimmune response in a type 1 diabetes mouse model
Transplanting allogeneic cells into a non-human primate without immune suppression represents a key step toward development of engineered cells for the treatment of disease
SEATTLE, June 17, 2022 (GLOBE NEWSWIRE) -- Sana Biotechnology, Inc. (NASDAQ: SANA), a company focused on creating and delivering engineered cells as medicines, presented data showing survival of transplanted allogeneic, hypoimmune cells of several different types in a variety of locations in non-human primates (NHPs). The transplanted cells were induced pluripotent stem cell (iPSC)-derived cardiomyocytes, retinal pigment epithelium (RPE) cells, and islet cells, which were engineered to include Sana’s hypoimmune gene modifications that enable immune evasion. Data were presented by Sonja Schrepfer, M.D., Ph.D., Head of Hypoimmune Platform at Sana, during sessions at the International Society for Stem Cell Research (ISSCR) 2022 Annual Meeting taking place from Wednesday, June 15 through Sunday, June 19 in San Francisco.
“These data, demonstrating that three types of transplanted cells are able to survive and function in NHPs without immunosuppression, highlight the transformative potential of Sana’s hypoimmune platform across a number of different cell types that can address a variety of diseases,” said Steve Harr, Sana’s President and Chief Executive Officer. “As an example, the use of allogeneic islet transplant has had limited success in treating type 1 diabetes due to morbidities from the necessary immunosuppression. In contrast, our data indicate that we successfully engineered HIP human pancreatic islet cells to evade immune recognition, and these cells persisted and normalized glucose levels in in vivo models. We are applying the hypoimmune platform to a number of programs in our pipeline, including SC291, our CD19 targeted allogeneic CAR T therapy for blood cancers, with a goal of an IND this year, and SC451, our islet cell program with a goal of an IND for the treatment of type 1 diabetes in 2023.”
Transplanting cells or tissues from a donor to a different recipient currently requires intense immunosuppression to prevent rejection of the transplant. Sana’s HIP platform goal is to eliminate the need for immunosuppression by cloaking cells from immune recognition. The platform includes disruption of the major histocompatibility (MHC) class I and MHC class II expression to hide cells from the adaptive immune system, which includes antibody and T cell responses. These changes alone make cells susceptible to innate immune cell killing, in particular by natural killer (NK) cells. However, Sana’s HIP platform additionally provides for evasion from innate cell killing, including via the overexpression of CD47, a molecule that protects HIP-modified cells from innate cell killing involving either NK cells or macrophages. HIP-modified pluripotent stem cells can serve as the starting material for the differentiation of specialized cell types to serve as cell-based therapeutics. Sana’s goal is to use these HIP-modified cells to replace damaged or missing cells in the body in a number of different diseases, including, among others, cancer, type 1 diabetes, and cardiac disease.
Survival of HIP-modified islet cells for type 1 diabetes
Primary NHP pancreatic islet cells
In this study, syngeneic or allogeneic mouse islet cells were transplanted intramuscularly without immunosuppression into diabetic autoimmune mice (n=15), split into three cohorts. The first cohort received unmodified syngeneic islet cells, the second cohort received unmodified allogeneic islet cells, and the third cohort received allogeneic HIP islet cells. The unmodified cells disappeared rapidly in the allogeneic setting (within 10 days) as well as in the syngeneic setting (within two weeks) due to autoimmune recognition. Neither cohort had a decrease in glucose levels. The HIP islet cells survived in all five diabetic mice for the duration of the study (one month at data lock), and glucose levels dropped, demonstrating therapeutic function of the HIP islet cells.
Survival of HIP-modified cardiomyocytes (iPSC-derived)
Survival of HIP-modified retinal pigmental epithelial (RPE) cells (iPSC-derived)
The HIP RPE survived in all three monkeys for the duration of the study (three weeks at data lock), and there was no evidence of a systemic immune response, including no T cell activation, antibody production, microglial or NK cell activity. Two weeks after the initial dose, the NHPs were re-injected with the same cell type into the second eye, so that the NHPs received a total of two doses. Unmodified WT RPEs again evoked a rapid systemic immune response in all NHPs, with activation of T cells and antibody production, and cells almost completely eliminate within one week. HIP RPE cells continued to survive even after re-injection without stimulation of adaptive or innate immune responses. These data suggest the potential to re-administer HIP RPE cells.
Sana intends to submit the data behind its presentations for publication in a peer-reviewed journal.
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