title: The pharmacology of second-generation chimeric antigen receptors.
abstract: Second-generation chimeric antigen receptors (CARs) retarget and reprogramme T cells to augment their antitumour efficacy. The combined activating and co-stimulatory domains incorporated in these CARs critically determine the function, differentiation, metabolism and persistence of engineered T cells. CD19-targeted CARs that incorporate CD28 or 4-1BB signalling domains are the best known to date. Both have shown remarkable complete remission rates in patients with refractory B cell malignancies. Recent data indicate that CD28-based CARs direct a brisk proliferative response and boost effector functions, whereas 4-1BB-based CARs induce a more progressive T cell accumulation that may compensate for less immediate potency. These distinct kinetic features can be exploited to further develop CAR-based T cell therapies for a variety of cancers. A new field of immunopharmacology is emerging.
authors.affiliation: 1] The Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA. [2] Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
authors.forename: Sjoukje J C
authors.initials: SJ
authors.lastname: van der Stegen
authors.affiliation: 1] The Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA. [2] Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Hamieh
authors.affiliation: 1] The Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA. [2] Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
authors.forename: Michel
authors.initials: M
authors.lastname: Sadelain
mesh_terms: D000818:Animals; D018106:CD28 Antigens / Q000276:immunology / Q000627:therapeutic use; D002678:Chimera; D006801:Humans; D007167:Immunotherapy / Q000379:methods* / Q000639:trends; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D011946:Receptors, Antigen / Q000276:immunology* / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018106:CD28 Antigens; D011946:Receptors, Antigen