title: Challenges to chimeric antigen receptor (CAR)-T cell therapy for cancer.
abstract: Chimeric antigen receptor (CAR)-expressing T cells have demonstrated potent clinical efficacy in patients with B cell malignancies. However, the use of CAR-T cell therapy targeting other cancers has, in part, been limited by both the induction of antigen-specific toxicities targeting normal tissues expressing the target-antigen, and the extreme potency of CAR-T cell treatments resulting in life-threatening cytokine-release syndromes. Herein, we discuss toxicities associated with CAR-T cell therapy in the clinic. Further, we discuss potential clinical interventions to ameliorate these toxicities and the application of preclinical animal models to predict the clinical utility of CAR-T cell therapy.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, 1020 Locust Street, JAH 368, Philadelphia, PA 19107, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Magee
authors.forename: Adam E
authors.initials: AE
authors.lastname: Snook
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D006801:Humans; D016219:Immunotherapy, Adoptive; D018448:Models, Immunological; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D011948:Receptors, Antigen, T-Cell