Stealth designs to overcome allorejection in engineered cell therapy

The rapid development of allogeneic engineered therapeutic cells has intensified the challenge of host immune-mediated rejection. Advances in molecular immunology, genetic engineering, and induced pluripotent stem cell-based multigene editing have enabled the creation of 'stealth' allogeneic cells designed to evade immune detection while maintaining function. Key strategies include the deletion of human leukocyte antigen class I and class II molecules to limit T cell recognition, the expression of natural killer (NK) cell inhibitory ligands to prevent NK cell-mediated killing, and the upregulation of CD47 to suppress phagocytosis. An expanding repertoire of immune-modulatory molecules, receptor-ligand interactions, and experimental assays is refining these approaches. Together, stealth designs are accelerating the translation of allogeneic cell therapies toward more durable and broadly applicable clinical use.