[Advances in immunotherapy of hematological malignancies by using chimeric antigen receptor-modified lymphocytes]

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2013 Apr;21(2):521-5. doi: 10.7534/j.issn.1009-2137.2013.02.056.
[Article in 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.

Publication types

  • English Abstract
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Cell- and Tissue-Based Therapy
  • Hematologic Neoplasms / therapy*
  • Humans
  • Immunotherapy*
  • Receptors, Antigen / immunology*
  • Recombinant Fusion Proteins / immunology*
  • T-Lymphocytes / immunology*

Substances

  • Receptors, Antigen
  • Recombinant Fusion Proteins