Clinical immunotherapy of B-cell malignancy using CD19-targeted CAR T-cells

Curr Gene Ther. 2014 Feb;14(1):35-43. doi: 10.2174/1566523213666131223130554.

Abstract

The CD19 molecule is ubiquitously expressed throughout all stages of B-cell differentiation, but is not found on haemopoietic stem cells. Since most B-cell leukaemias and lymphomas retain CD19 expression, it represents an excellent target for immunotherapy of these malignant disorders. Over the past 10 years, compelling pre-clinical evidence has accrued to indicate that expression of a CD19-targeted chimeric antigen receptor (CAR) in peripheral blood T-cells exerts therapeutic efficacy in diverse models of B-cell malignancy. Building on this, clinical studies are ongoing in several centres in which autologous CD19-specific CAR T-cells are undergoing evaluation in patients with acute and chronic B-cell leukaemia and refractory lymphoma. Early data have generated considerable excitement, providing grounds to speculate that CAR-based immunotherapy will radically alter existing management paradigms in B-cell malignancy. The focus of this mini-review is to evaluate these emerging clinical data and to speculate on clinical prospects for this new therapeutic modality.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antigens, CD19 / immunology
  • Antigens, CD19 / therapeutic use
  • B-Lymphocytes / immunology
  • Genetic Therapy*
  • Humans
  • Immunotherapy, Adoptive*
  • Lymphocyte Activation / immunology
  • Lymphoma, B-Cell / genetics
  • Lymphoma, B-Cell / immunology*
  • Lymphoma, B-Cell / therapy
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / therapeutic use*
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / therapeutic use

Substances

  • Antigens, CD19
  • Receptors, Antigen, T-Cell
  • Recombinant Fusion Proteins