HLA-homozygous iPSC-cardiomyocytE Aggregate manufacturing technoLogies for allogenic cell therapy to the heart (HEAL)

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HEAL will focus on general bottlenecks to induced pluripotent stem cell therapies with a particular focus on heart failure, which remains a major cause of morbidity and mortality with very few treatment options. HLA-homozygous cell line derived cardiomyocyte aggregates offer the prospect of a restorative heart therapy applicable to large patient populations and to overcome economic barriers associated with autologous approaches. By developing solutions for their mass-production and cryopreservation we will enable allogeneic treatment with minimum requirements for immunosuppression. Assays for assessment of immunogenicity will provide data for the development of an artificial intelligence powered algorithm to predict recipients' immune responses for personalised design of immunosuppression protocols. A potency assay to assure product effectiveness will be developed together with assays of tumorigenicity in vitro and in vivo that meet and exceed current regulatory requirements. A genetic integrity pipeline defining the most sensitive assays for rigorous assessment will be developed and a rescue tool in the form of a biallelic suicide gene for programmed cell death will add to the safety toolbox for the therapy. Optimisation of cell-product administration in terms of retention and engraftment, including catheter-based delivery as minimally invasive alternative to surgical application, and assessment of risks of graft-induced arrhythmia will be determined in a pig model. Early dialogues, via established links, to the regulatory authorities will ensure proper development according to GMP requirements. Freedom to operate and licensing strategies with a health technology and infrastructure assessment of European centres will set the scene for approval of the cell product and related assays and protocols for storage and distribution required to progress towards a first in man study of cell-based heart repair.