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CD229 CAR T cells eliminate multiple myeloma and tumor propagating cells without fratricide. 2020
Sabarinath V Radhakrishnan, and
Tim Luetkens, and
Sandra D Scherer, and
Patricia Davis, and
Erica R Vander Mause, and
Michael L Olson, and
Sara Yousef, and
Jens Panse, and
Yasmina Abdiche, and
K David Li, and
Rodney R Miles, and
William Matsui, and
Alana L Welm, and
Djordje Atanackovic
Multiple Myeloma Program & Cancer Immunotherapy, Division of Hematology and Hematologic Malignancies, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, 84112, USA.
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.
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