Nature: CD229 CAR T Cells Eliminate Multiple Myeloma and Tumor Propagating Cells Without Fratricide

Nat Commun. 2020 Feb 7;11(1):798. doi: 10.1038/s41467-020-14619-z

Radhakrishnan SV, Luetkens T, Scherer SD, Davis P, Vander Mause ER, Olson ML, Yousef S, Panse J, Abdiche Y, Li KD, Miles RR, Matsui W, Welm AL, Atanackovic D

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 down regulated in T cells during activation. In addition, while CD229 CAR T cells target normal CD229^high T cells, they spare functional CD229^neg/low T cells. These findings indicate that CD229 CAR T cells may be an effective treatment for patients with MM.