Review: Current clinical applications of chimeric antigen receptor (CAR) modified T cells.
The past several years have been marked by extraordinary advances in clinical applications of immunotherapy. In particular, adoptive cellular therapy utilizing chimeric antigen receptor (CAR)-modified T cells targeted to CD19 has demonstrated substantial clinical efficacy in children and adults with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) and durable clinical benefit in a smaller subset of patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or B-cell non-Hodgkin lymphoma (B-NHL). Early-phase clinical trials are currently assessing CAR T-cell safety and efficacy in additional malignancies. Here, we discuss clinical results from the largest series to date investigating CD19-targeted CAR T cells in B-ALL, CLL, and B-NHL, including discussion of differences in CAR T-cell design and production and treatment approach, as well as clinical efficacy, nature of severe cytokine release syndrome and neurologic toxicities, and CAR T-cell expansion and persistence. We additionally review the current and forthcoming use of CAR T cells in multiple myeloma and several solid tumors and highlight challenges and opportunities afforded by the current state of CAR T-cell therapies, including strategies to overcome inhibitory aspects of the tumor microenvironment and enhance antitumor efficacy.
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Mark B
MB
Geyer
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: brentjer@mskcc.org.
Renier J
RJ
Brentjens
D000818:Animals; D002986:Clinical Trials as Topic; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D011948:Receptors, Antigen, T-Cell
CAR T cells; acute lymphoblastic leukemia; adoptive cellular therapy; chimeric antigen receptors; cytokine release syndrome