CD229 CAR T cells eliminate multiple myeloma and tumor propagating cells without fratricide
Sabarinath Venniyil Radhakrishnan, Tim Luetkens, Sandra D. Scherer, Patricia M. Davis, Erica R. Vander Mause, Michael Olson, Sara Yousef, Jens Panse, Yasmina Abdiche, K. David Li, Rodney R. Miles, William Matsui, Alana L. Welm, Djordje Atanackovic
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 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.