title: Seatbelts in CAR therapy: How Safe Are CARS?
abstract: T-cells genetically redirected with a chimeric antigen receptor (CAR) to recognize tumor antigens and kill tumor cells have been infused in several phase 1 clinical trials with success. Due to safety concerns related to on-target/off-tumor effects or cytokine release syndrome, however, strategies to prevent or abate serious adverse events are required. Pharmacologic therapies; suicide genes; or novel strategies to limit the cytotoxic effect only to malignant cells are under active investigations. In this review, we summarize results and toxicities of investigations employing CAR redirected T-cells, with a focus on published strategies to grant safety of this promising cellular application.
authors.affiliation: Bone Marrow Transplantation and Cellular Therapy, University of Alabama at Birmingham, Birmingham, AL 35294-3300, USA. kminagawa@uabmc.edu.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Minagawa
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030-2399, USA. xxzhou@txch.org.
authors.forename: Xiaoou
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Bone Marrow Transplantation and Cellular Therapy, University of Alabama at Birmingham, Birmingham, AL 35294-3300, USA. smineishi@uabmc.edu.
authors.forename: Shin
authors.initials: S
authors.lastname: Mineishi
authors.affiliation: Bone Marrow Transplantation and Cellular Therapy, University of Alabama at Birmingham, Birmingham, AL 35294-3300, USA. adistasi@uabmc.edu.
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Stasi
keywords: adoptive immunotherapy; cell therapy; chimeric antigen receptor; safety switch; suicide gene