Synthetic immune checkpoint engagers protect HLA-deficient iPSCs and derivatives from innate immune cell cytotoxicity

We present a new class of agonistic immune checkpoint engagers that protect human leukocyte antigen (HLA)-depleted induced pluripotent stem cell-derived endothelial cells (iECs) from innate immune cells. Engagers with agonistic functionality to their inhibitory receptors TIM3 and SIRPα effectively protect engineered iECs from natural killer (NK) cell and macrophage killing. The SIRPα engager can be combined with truncated CD64 to generate fully immune evasive iECs capable of escaping allogeneic cellular and immunoglobulin G (IgG) antibody-mediated rejection. Synthetic immune checkpoint engagers have high target specificity and lack retrograde signaling in the engineered cells. This modular design allows for the exploitation of more inhibitory immune pathways for immune evasion and could contribute to the advancement of allogeneic cell therapeutics.PMID:37922880 | DOI:10.1016/j.stem.2023.10.003

Source: Cell Stem Cell - November 3, 2023 Category: Stem Cells Authors: Alessia Gravina Grigol Tediashvili Yueting Zheng Kumiko A Iwabuchi Sara M Peyrot Susan Z Roodsari Lauren Gargiulo Shin Kaneko Mitsujiro Osawa Sonja Schrepfer Tobias Deuse Source Type: research