Genetically engineered hypoimmunogenic cell therapy

Immune rejection is an important obstacle to the use of allogeneic ‘off-the-shelf’ cells for transplantation into immunocompetent patients. Genetic modification has emerged as a promising approach to improve immune compatibility in various applications, including cancer immunotherapy and stem cell-based therapies. Several approaches have been proposed to evade the recognition and attack of transplanted cells by specific host immune cells; however, further investigation is needed to ensure the hypoimmunity and safety of cell-based therapies in clinical practice. This Review discusses key advances and challenges in the clinical translation of hypoimmunogenic cells and describes the genetic engineering methods and manufacturing processes used to create hypoimmunogenic therapeutic cells, while highlighting the complexity of relevant immunological pathways.