The BETA-Protect collaboration aims to develop and refine personalised immunomodulatory strategies to prevent alloimmune rejection of human regenerative cellular therapies for type 1 diabetes.
It brings together unparalleled infrastructure and leading expertise from the UK in alloimmunity, autoimmunity, immunotherapy and regenerative medicine that is essential to address questions that are fundamental to the clinical translation of cellular therapies for type 1 diabetes.
Using pancreatic islets as controls, the collaboration will utilise experimental models of the human immune compartment to compare the immunogenicity of allogeneic (non-self) and autologous (self) insulin-producing β-like cells. In Phase I of the research programme, insulin producing β-like cells will be generated from human induced pluripotent stem cells. Other sources of insulin-producing cells under investigation by BETA-Protect collaborators include pancreatic organoids and exocrine pancreatic cells.
BETA-Protect will compare the efficacy of leading immunotherapies, used alone or in combination, in suppression of the alloimmune response to regenerative cellular therapies for diabetes. In Phase I of the research programme, the efficacy of polyclonal and allospecific regulatory T cells will be examined. Other immunomodulation strategies, such as myeloid derived suppressor cells, are also under investigation by BETA-Protect collaborators.
The innate and adaptive cellular and humoral immune responses will be quantified using a comprehensive panel of in vivo and in vitro immunological and histopathological assays, while loss of human insulin production and normoglycaemia in experimental models of diabetes will serve as additional functional end-points.
The proposed programme is anticipated to provide definitive data to directly inform the design and conduct of clinical trials on the adjunct use of immunotherapies and β-like cellular therapies.