CD229 CAR T cells eliminate multiple myeloma and tumor propagating cells without fratricide

Sabarinath V. Radhakrishnan, Tim Luetkens (), Sandra D. Scherer, Patricia Davis, Erica R. Vander Mause, Michael L. Olson, Sara Yousef, Jens Panse, Yasmina Abdiche, K. David Li, Rodney R. Miles, William Matsui, Alana L. Welm and Djordje Atanackovic
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Sabarinath V. Radhakrishnan: University of Utah
Tim Luetkens: University of Utah
Sandra D. Scherer: University of Utah
Patricia Davis: University of Utah and ARUP Laboratories
Erica R. Vander Mause: University of Utah
Michael L. Olson: University of Utah
Sara Yousef: University of Utah
Jens Panse: University Hospital RWTH Aachen
Yasmina Abdiche: Carterra Inc.
K. David Li: University of Utah and ARUP Laboratories
Rodney R. Miles: University of Utah and ARUP Laboratories
William Matsui: The University of Texas at Austin
Alana L. Welm: University of Utah
Djordje Atanackovic: University of Utah

Nature Communications, 2020, vol. 11, issue 1, 1-9

Abstract: Abstract Multiple myeloma (MM) is a plasma cell malignancy and most patients eventually succumb to the disease. Chimeric antigen receptor (CAR) T cells targeting B-Cell Maturation Antigen (BCMA) on MM cells have shown high-response rates, but limited durability. CD229/LY9 is a cell surface receptor present on B and T lymphocytes that is universally and strongly expressed on MM plasma cells. Here, we develop CD229 CAR T cells that are highly active in vitro and in vivo against MM plasma cells, memory B cells, and MM-propagating cells. We do not observe fratricide during CD229 CAR T cell production, as CD229 is downregulated in T cells during activation. In addition, while CD229 CAR T cells target normal CD229high T cells, they spare functional CD229neg/low T cells. These findings indicate that CD229 CAR T cells may be an effective treatment for patients with MM.

Date: 2020
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DOI: 10.1038/s41467-020-14619-z

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