Expanding Therapeutic Strategies for Chimeric Antigen Receptor T Cells

A wide range of autologous and allogeneic immune cells bearing diverse chimeric antigen receptors (CARs) have been prepared to treat B cell and other hematological malignancies, some solid tumors, autoimmune diseases, graft vs host disorders, and transplantation rejection. Therapeutic CAR immune cells bearing a specifically designed CAR that binds a target cell antigen home precisely to those target cells and signal alterations in their functions. The longest successful and now US Food and Drug Administration-approved experience is with 6 systems of CAR T cells recognizing malignant B cell surface antigens CD19 or B cell maturation antigen. Chimeric antigen receptor constructs in CAR immune cell systems have been improved in multiple ways to increase persistence at lesions, minimize off-target effects, and enhance cytotoxic or immunosuppressive effectiveness. Acute side effects, such as adverse responses to CAR immune cell-derived cytokines and neurological disorders, are common but have been reduced by elevated expression of cytokine receptors on CAR immune cells. Allogeneic CAR immune cells from normal donors may evoke graft vs host reactions. Future improvements, including messenger ribonucleic acid editing of metabolic messages to minimize CAR T cell exhaustion and viral approaches to creating autologous CAR T cells in vivo, will improve future therapeutic effectiveness and safety.