Chimeric Antigen Receptor T Cells Targeting CD79b Show Efficacy in Lymphoma with or without Cotargeting CD19

Clin Cancer Res. 2019 Dec 1;25(23):7046-7057. doi: 10.1158/1078-0432.CCR-19-1337. Epub 2019 Aug 22.


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+, CD19-, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD19 / immunology*
  • Apoptosis
  • CD79 Antigens / immunology*
  • Cell Proliferation
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Lymphocyte Activation
  • Lymphoma, Mantle-Cell / immunology
  • Lymphoma, Mantle-Cell / metabolism
  • Lymphoma, Mantle-Cell / therapy*
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Prognosis
  • Receptors, Chimeric Antigen / immunology*
  • T-Lymphocytes / immunology*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays


  • Antigens, CD19
  • CD19 molecule, human
  • CD79 Antigens
  • CD79B protein, human
  • Receptors, Chimeric Antigen