A T-cell-directed chimeric antigen receptor for the selective treatment of T-cell malignancies

Blood. 2015 Aug 20;126(8):983-92. doi: 10.1182/blood-2015-02-629527. Epub 2015 Jun 8.


Options for targeted therapy of T-cell malignancies remain scarce. Recent clinical trials demonstrated that chimeric antigen receptors (CARs) can effectively redirect T lymphocytes to eradicate lymphoid malignancies of B-cell origin. However, T-lineage neoplasms remain a more challenging task for CAR T cells due to shared expression of most targetable surface antigens between normal and malignant T cells, potentially leading to fratricide of CAR T cells or profound immunodeficiency. Here, we report that T cells transduced with a CAR targeting CD5, a common surface marker of normal and neoplastic T cells, undergo only limited fratricide and can be expanded long-term ex vivo. These CD5 CAR T cells effectively eliminate malignant T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoma lines in vitro and significantly inhibit disease progression in xenograft mouse models of T-ALL. These data support the therapeutic potential of CD5 CAR in patients with T-cell neoplasms.

Publication types

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

MeSH terms

  • Animals
  • Antigens, Neoplasm / immunology*
  • CD5 Antigens / immunology*
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Mice
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / immunology*
  • Receptors, Antigen, T-Cell / immunology*
  • Transduction, Genetic
  • Transplantation Chimera
  • Xenograft Model Antitumor Assays


  • Antigens, Neoplasm
  • CD5 Antigens
  • Receptors, Antigen, T-Cell