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Clin Cancer Res. 2019 Aug 22. pii: clincanres.1337.2019. doi: 10.1158/1078-0432.CCR-19-1337. [Epub ahead of print]

Chimeric antigen receptor T cells targeting CD79b show efficacy in lymphoma with or without co-targeting CD19.

Author information

1
Clinical Immunology, University of Southern Denmark.
2
Cancer Center, Massachusetts General Hospital, Harvard Medical School.
3
Cancer Center, Massachusetts General Hospital.
4
Duke University.
5
Neurosurgery, Massachusetts General Hospital.
6
Cancer and Inflammation Research, University of Southern Denmark.
7
Haematology, Odense University Hospital.
8
Hematology, Aarhus University Hospital.
9
Department of Cancer and Inflammation Research, University of Southern Denmark.
10
Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark.
11
Medical Oncology, Dana-Farber Cancer Institute.
12
Clinical Immunology, Odense University Hospital.
13
Bone Marrow Transplant/Cellular Therapy, Massachusetts General Hospital.
14
Cancer Center, Massachusetts General Hospital, Harvard Medical School mvmaus@mgh.harvard.edu.

Abstract

PURPOSE:

T cells engineered to express a chimeric antigen receptor (CAR) against CD19 have recently been FDA-approved for the treatment of relapsed or refractory large B cell lymphoma. Despite the success and curative potential of CD19 CAR T cells, several reports describing disease relapse due to antigen loss are now emerging.

EXPERIMENTAL DESIGN:

We developed a novel CAR construct directed against CD79b, a critical receptor for successful B cell development that remains highly expressed in several subtypes of B cell lymphoma, including mantle cell lymphoma (MCL). We tested CAR T cells directed against CD79b alone or in combination with CD19 targeting in a single construct, against cell line- and patient-derived xenograft models.

RESULTS:

We demonstrate CAR79b antigen-specific recognition and cytotoxicity against a panel of cell lines and patient-derived xenograft models of MCL. Importantly, we show that downregulation of CD19 does not influence surface expression of CD79b and that anti-CD79b CAR T cells alone or arranged in a dual-targeting format with a CD19 single-chain variable fragment (scFv) are able to recognize and eliminate CD19-positive, CD19-negative, and mixed CD19+/CD19- B cell lymphoma.

CONCLUSIONS:

Our findings demonstrate that CAR T cells targeting CD79b alone or in combination have promise for treating and preventing CD19 antigen escape in B cell lymphomas.

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