Advances in immunotherapy of hematological malignancies by using chimeric antigen receptor-modified lymphocytes.
10.7534/j.issn.1009-2137.2013.02.056
- Author:
Xiao-Jun XU
1
;
Hai-Zhao ZHAO
;
Yong-Min TANG
Author Information
1. Department of Hematology and Oncology, Children's Hospital of Zhejiang University School of Medicine, Zhejiang Province, China.
- Publication Type:Journal Article
- MeSH:
Cell- and Tissue-Based Therapy;
Hematologic Neoplasms;
therapy;
Humans;
Immunotherapy;
Receptors, Antigen;
immunology;
Recombinant Fusion Proteins;
immunology;
T-Lymphocytes;
immunology
- From:
Journal of Experimental Hematology
2013;21(2):521-525
- CountryChina
- Language:Chinese
-
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.
