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

Irene Scarfò, Maria Ormhøj, Matthew J. Frigault, Ana P. Castano, Selena Lorrey, Amanda A. Bouffard, Alexandria van Scoyk, Scott J. Rodig, Alexandra J. Shay, Jon C. Aster, Frederic I. Preffer, David M. Weinstock and Marcela V. Maus

Key points

  • CD37 CAR T cells undergo activation, proliferation, and cytokine production in response to CD37 engagement alone and in bispecific format.

  • Anti-CD37 CAR T cells have anti-tumor activity against B and T cell lymphomas without fratricide.

Abstract

Chimeric antigen receptor (CAR) T cells have emerged as a novel form of treatment for patients with B-cell malignancies. In particular, anti-CD19 CAR T-cell therapy has effected impressive clinical responses in B-cell acute lymphoblastic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL). 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 (CLL) and in some cases of cutaneous and peripheral T-cell lymphomas (CTCL and PTCL, respectively). 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.

  • Submitted April 4, 2018.
  • Accepted August 3, 2018.