Advances in T-cell therapy for ALL

Best Pract Res Clin Haematol. 2014 Sep-Dec;27(3-4):222-8. doi: 10.1016/j.beha.2014.10.014. Epub 2014 Oct 27.

Abstract

CD19-directed chimeric antigen receptor T cells (CART19 or CTL019) have been used with success in pediatric and adult acute lymphocytic leukemia (ALL) and chronic lymphocytic leukemia (CLL) patients. While this therapy has caused toxicities, including cytokine release syndrome and macrophage activation syndrome, these conditions are reversible with IL-6 blockade using the monoclonal antibody tocilizumab. Furthermore, 90% of the very high-risk patients who underwent infusion with CTL019 achieved a complete response, despite the fact that they previously failed multiple therapies and/or transplant. With improved cell persistence, this immunotherapy may one day prove to be more than a bridge to transplant and may in fact be a transplant alternative.

Keywords: ALL; CLL; IL-6; acute lymphocytic leukemia; chimeric antigen receptor; chronic lymphocytic leukemia; cytokine release syndrome; macrophage activation syndrome.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Humans
  • Immunotherapy / methods*
  • Interleukin-6 / antagonists & inhibitors*
  • Interleukin-6 / immunology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Receptors, Antigen, T-Cell*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / transplantation*

Substances

  • Antibodies, Monoclonal, Humanized
  • CTL019 chimeric antigen receptor
  • IL6 protein, human
  • Interleukin-6
  • Receptors, Antigen, T-Cell
  • tocilizumab