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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Scarfò, I; Ormhøj, M; Frigault, MJ; Castano, AP; Lorrey, S; Bouffard, AA; van Scoyk, A; Rodig, SJ; Shay, AJ; Aster, JC; Preffer, FI; Weinstock, DM; Maus, MV

Published Date

  • October 2018

Published In

Volume / Issue

  • 132 / 14

Start / End Page

  • 1495 - 1506

PubMed ID

  • 30089630

Pubmed Central ID

  • 30089630

Electronic International Standard Serial Number (EISSN)

  • 1528-0020

International Standard Serial Number (ISSN)

  • 0006-4971

Digital Object Identifier (DOI)

  • 10.1182/blood-2018-04-842708

Language

  • eng