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Stealth designs to overcome allorejection in engineered cell therapy
Yan-Ruide Li1, Yuning Chen2, Lili Yang3
1Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA; Goodman-Luskin Microbiome Center, Los Angeles, CA 90095, USA.
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.
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.
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