Toxicity and management in CAR T-cell therapy.
T cells can be genetically modified to target tumors through the expression of a chimeric antigen receptor (CAR). Most notably, CAR T cells have demonstrated clinical efficacy in hematologic malignancies with more modest responses when targeting solid tumors. However, CAR T cells also have the capacity to elicit expected and unexpected toxicities including: cytokine release syndrome, neurologic toxicity, "on target/off tumor" recognition, and anaphylaxis. Theoretical toxicities including clonal expansion secondary to insertional oncogenesis, graft versus host disease, and off-target antigen recognition have not been clinically evident. Abrogating toxicity has become a critical step in the successful application of this emerging technology. To this end, we review the reported and theoretical toxicities of CAR T cells and their management.
Department of Pediatrics and Communicable Diseases, University of Michigan , Ann Arbor, Michigan, USA.
Challice L
CL
Bonifant
Department of Medicine, Memorial Sloan Kettering Cancer Center , New York, New York, USA.
Hollie J
HJ
Jackson
Department of Medicine, Memorial Sloan Kettering Cancer Center , New York, New York, USA.
Renier J
RJ
Brentjens
Department of Pediatrics, Memorial Sloan Kettering Cancer Center , New York, New York, USA.
Kevin J
KJ
Curran