title: [Advances in immunotherapy of hematological malignancies by using chimeric antigen receptor-modified lymphocytes].
abstract: Chimeric antigen receptors (CAR) are fusion proteins between single-chain variable fragments (scFv) from monoclonal antibodies and signaling domains of T-cells, which allow T-cells recognize specific cell-surface targets in an MHC-unrestricted fashion. The structure of CAR has changed over time, from first generation CAR (scFv + signaling moiety) to 2 and 3 generation CAR (combined with one or multiple costimulatory endodomains, such as CD28, 4-1BB and OX40), which enhance persistence, expansion and cytotoxicity of CAR. Many clinical trials treating hematological malignancies using the CAR-modified T-cells targeting CD19 and CD20 are under evaluation or even finished. These clinical trials indicated that CAR-based immunotherapy prolonged the survival of patients with relapsed/refractory B-cell malignancies. Furthermore, CAR have being studied to translate to other fields like adoptive therapy after hematopoietic stem cell transplantation. As to the treatment toxicity, CAR modified T-cell infusion is tolerant and safe in most patients. However, insertional mutagenesis, off-target effect and inflammatory response are safety issues surrounding CAR-modified T-cell therapy. In this review, the use of CAR technique in treatment of hematologic malignancies and evaluation of CAR safety are summarized.
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Zhejiang University School of Medicine, Zhejiang Province, China.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Xu
authors.forename: Hai-Zhao
authors.initials: HZ
authors.lastname: Zhao
authors.forename: Yong-Min
authors.initials: YM
authors.lastname: Tang
mesh_terms: D064987:Cell- and Tissue-Based Therapy; D019337:Hematologic Neoplasms / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy; D011946:Receptors, Antigen / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D011946:Receptors, Antigen; D011993:Recombinant Fusion Proteins