Anti-CD37 chimeric antigen receptor T cells are active against B- and T-cell lymphomas

Blood. 2018 Oct 4;132(14):1495-1506. doi: 10.1182/blood-2018-04-842708. Epub 2018 Aug 8.


Chimeric antigen receptor (CAR) T cells have emerged as a novel form of treatment of patients with B-cell malignancies. In particular, anti-CD19 CAR T-cell therapy has effected impressive clinical responses in B-cell acute lymphoblastic leukemia and diffuse large B-cell lymphoma. However, not all patients respond, and relapse with antigen loss has been observed in all patient subsets. Here, we report on the design and optimization of a novel CAR directed to the surface antigen CD37, which is expressed in B-cell non-Hodgkin lymphomas, in chronic lymphocytic leukemia, and in some cases of cutaneous and peripheral T-cell lymphomas. We found that CAR-37 T cells demonstrated antigen-specific activation, cytokine production, and cytotoxic activity in models of B- and T-cell lymphomas in vitro and in vivo, including patient-derived xenografts. Taken together, these results are the first showing that T cells expressing anti-CD37 CAR have substantial activity against 2 different lymphoid lineages, without evidence of significant T-cell fratricide. Furthermore, anti-CD37 CARs were readily combined with anti-CD19 CARs to generate dual-specific CAR T cells capable of recognizing CD19 and CD37 alone or in combination. Our findings indicate that CD37-CAR T cells represent a novel therapeutic agent for the treatment of patients with CD37-expressing lymphoid malignancies.

Publication types

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

MeSH terms

  • Animals
  • Antigens, Neoplasm / analysis
  • Antigens, Neoplasm / immunology*
  • Cell Line, Tumor
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Lymphoma, B-Cell / immunology
  • Lymphoma, B-Cell / pathology
  • Lymphoma, B-Cell / therapy*
  • Lymphoma, T-Cell / immunology
  • Lymphoma, T-Cell / pathology
  • Lymphoma, T-Cell / therapy*
  • Mice
  • Receptors, Chimeric Antigen / immunology
  • Receptors, Chimeric Antigen / therapeutic use
  • T-Lymphocytes / immunology
  • T-Lymphocytes / transplantation
  • Tetraspanins / analysis
  • Tetraspanins / antagonists & inhibitors
  • Tetraspanins / immunology*


  • Antigens, Neoplasm
  • CD37 protein, human
  • Receptors, Chimeric Antigen
  • Tetraspanins