Targeting T Cell Malignancies Using CD4CAR T-Cells and Implementing a Natural Safety Switch

Stem Cell Rev Rep. 2019 Jun;15(3):443-447. doi: 10.1007/s12015-019-09876-5.

Abstract

T cell malignancies are aggressive diseases with no standard treatment available, often resulting in poor patient outcomes. Lately, the recent FDA approval of a CD19 CAR T cell therapy for B cell acute lymphoblastic leukemia has earned nationwide attention, leading to the possibility that success of CD19 CAR therapy can be extended to T cell malignancies. However, the impact of T cell depletion due to a shared antigen pool remains an issue to be resolved. Here, we describe a CD4CAR capable of eliminating CD4-positive T cell acute lymphoblastic leukemia in a systemic mouse model, with CAMPATH (alemtuzumab) as a natural safety switch to deplete the infused CD4CAR T cells to prevent toxicities associated with CD4 cell aplasia. Our data support the potential use of CD4CAR T cells for the treatment of CD4-postive T-cell acute lymphoblastic leukemia malignancies or refractory disease in clinical settings.

Keywords: Alemtuzumab; Anti-CD4 CAR; CAMPATH; Immunotherapy; T cell malignancies; T-cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alemtuzumab / pharmacology*
  • Animals
  • CD4-Positive T-Lymphocytes* / pathology
  • CD4-Positive T-Lymphocytes* / transplantation
  • Humans
  • Immunotherapy, Adoptive*
  • Jurkat Cells
  • Male
  • Mice
  • Mice, Inbred NOD
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma* / pathology
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma* / therapy
  • Xenograft Model Antitumor Assays

Substances

  • Alemtuzumab