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

Autor:	Scarfò I; Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Charlestown, MA.; Harvard Medical School, Boston, MA., Ormhøj M; Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Charlestown, MA.; Department of Clinical Immunology, Odense University Hospital, University of Southern Denmark, Odense, Denmark., Frigault MJ; Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Charlestown, MA.; Harvard Medical School, Boston, MA., Castano AP; Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Charlestown, MA., Lorrey S; Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Charlestown, MA., Bouffard AA; Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Charlestown, MA., van Scoyk A; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA., Rodig SJ; Department of Pathology, Brigham and Women's Hospital, Boston, MA., Shay AJ; Department of Pathology, Massachusetts General Hospital, Boston, MA; and., Aster JC; Harvard Medical School, Boston, MA.; Department of Pathology, Brigham and Women's Hospital, Boston, MA., Preffer FI; Harvard Medical School, Boston, MA.; Department of Pathology, Massachusetts General Hospital, Boston, MA; and., Weinstock DM; Harvard Medical School, Boston, MA.; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA., Maus MV; Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Charlestown, MA.; Harvard Medical School, Boston, MA.; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2018 Oct 04; Vol. 132 (14), pp. 1495-1506. Date of Electronic Publication: 2018 Aug 08.
DOI:	10.1182/blood-2018-04-842708
Abstrakt:	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. (© 2018 by The American Society of Hematology.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu