SBIR Phase I: Off-the-Shelf immuno-compatible cell therapies

The broader impact of this Small Business Innovation Research (SBIR) Phase I project is to improve cell therapy by enabling the rapid development of novel and safe therapies through the seamless production of pre-characterized, good manufacturing practice (GMP) grade, universally immune-compatible induced pluripotent stem cell (iPSC) cell lines. The solution will target the global cell therapy market, expected to be the fastest-growing sector in the regenerative medicine industry and reaching $9.8 B by 2026. This project will advance a technology for better clinical trials. This Small Business Innovation Research (SBIR) Phase I project explores feasibility of a platform for the generation of completely immune-compatible Off-The-Shelf cell therapies. The platform employs a fully scalable workflow centered on master induced pluripotent cell lines engineered for universal immune-compatibility. Cells are further functionalized by site-specific insertion of bacterial integrase receiver sites enabling safe and reliable insertion of new DNA constructs into defined genomic loci with low risk for off-target events. This approach will produce immune-compatible iPSC Receiver Cells that can be differentiated into many different mature cell types for use in cell therapy applications. The proposed activities will validate a new approach to prevent host-versus-grafts rejections based on the disruption of chaperone proteins that impair major histocompatibility complex (MHC)-1 function without eliminating MHC-1 cell-surface expression. Several iPSC cell lines will be generated and tested in vitro and in vivo to investigate the efficacy of the proposed method to prevent HLA-dependent cytotoxic T cell “non-self” and NK cell “missing-self” responses. The ability of the generated iPSC to generate differentiated immune-compatible cell lines will be assessed, validating the entire workflow of the proposed platform. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.