title: 4-1BB chimeric antigen receptors.
abstract: In addition to T-cell receptor signals, T lymphocytes require costimulatory signals for robust activation. Among these, those mediated by 4-1BB (CD137, TNFRSF9) are critical for tumor immunity. 4-1BB is expressed in T-cell receptor-activated lymphocytes as well as natural killer cells and other hematopoietic and nonhematopoietic cells. 4-1BB ligation induces a signaling cascade that results in cytokine production, expression of antiapoptotic molecules, and enhanced immune responses. In line with the described function of 4-1BB, its addition to CD3ζ chimeric antigen receptors (CARs) increases their capacity to provoke T-cell expansion and antitumor activity. The results of preclinical studies with 4-1BB CARs have been corroborated by encouraging results from clinical trials. Advantages and disadvantages of 4-1BB CARs versus CARs bearing other costimulatory components remain to be fully elucidated. In this review, we discuss the properties of 4-1BB, the design of 4-1BB CARs, and the function of T lymphocytes and natural killer cells expressing them.
authors.affiliation: From the Departments of *Pediatrics and †Physiology, National University of Singapore, Singapore; and ‡Department of Pediatrics, Niigata University, Niigata, Japan.
authors.forename: Dario
authors.initials: D
authors.lastname: Campana
authors.forename: Herbert
authors.initials: H
authors.lastname: Schwarz
authors.forename: Chihaya
authors.initials: C
authors.lastname: Imai
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive; D008213:Lymphocyte Activation / Q000276:immunology; D009369:Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D011948:Receptors, Antigen, T-Cell; C505714:TNFRSF9 protein, human; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9