Novel Immunotherapy for Multiple Myeloma: CAR T Cells Targeting CD229
Posted: Thursday, April 16, 2020
According to research findings initially slated for presentation at the 2020 NCCN Annual Conference (Abstract YIA20-003) and published in JNCCN–Journal of the National Comprehensive Cancer Network, manufactured chimeric antigen receptor (CAR) T cells that target CD229 SLAM receptors appear to be active in treating multiple myeloma and the disease’s tumor-propagating cells. These CAR T cells demonstrated limited fratricide during cell production, spared the functional CD229-negative and low T-cell population, and reduced antibody affinity, concluded Tim Luetkins, MD, of the University of Utah, Salt Lake City, and colleagues.
In this study, the investigators developed reportedly the first fully human antibody, clone 2D3, to target CD229 receptors. The antibody and T cells expressing CAR T cells were evaluated using various screening assays as well as biochemical characterization and functional assays.
Among the 20 patients with newly diagnosed and relapsed or refractory multiple myeloma evaluated, 2D3 bonded strongly with all of the patients’ CD229 CAR T cells, specifically killing CD229-expressing cells, and demonstrated activity against multiple myeloma and primary plasma cell leukemia cells. These CAR T cells also eliminated memory B cells, in contrast to B-cell maturation antigen (BCMA) CAR T cells.
Additionally, patients treated with CD229 CAR T cells experienced a reduction in the colony formation of CD34-negative bone marrow cells, compared with patients treated with BCMA CAR T cells. In vivo treatment with a single dose of CD229 CAR T cells resulted in tumor eradication or delayed tumor growth and “significantly prolonged survival,” the authors noted.
“To further reduce the targeting of normal T cells, we generated low-affinity CD229 antibodies and showed that CAR T cells based on these antibodies have increased selectivity for multiple myeloma cells over normal T cells,” the authors added.
Disclosure: The study authors reported no conflicts of interest.
