Toward “off-the-shelf” allogeneic CAR T cells

Chimeric antigen receptor (CAR) T cell therapy represents a major breakthrough in the field of immuno-oncology. Many potential issues are apparent for autologous CAR T cell therapy, such as time for manufacturing and need for interim therapies in progressing patients, wide variations in terms of quality and quantity of T cells, and difficulty to obtain enough cells for redosing. “Off-the-shelf” allogeneic CAR T cells premanufactured from third-party donors may theoretically provide solutions to these different problems. However, allogeneic T cells possess foreign immunological identities that can lead to histocompatibility considerations such as graft-versus-host disease and rejection of allogeneic cells. This review outlines the major recent advances for off-the-shelf T cell therapies currently in clinical trials or in preclinical development and describes strategies for reengineering or selecting specific T cell immune identities to create safe and efficient immunotherapies for patients.