CD229 CAR T cells eliminate multiple myeloma and tumor propagating cells without fratricide.
Sabarinath V RadhakrishnanTim LuetkensSandra D SchererPatricia DavisErica R Vander MauseMichael L OlsonSara YousefJens PanseYasmina AbdicheK David LiRodney R MilesWilliam MatsuiAlana L WelmDjordje AtanackovicPublished in: Nature communications (2020)
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.
Keyphrases
- induced apoptosis
- cell cycle arrest
- multiple myeloma
- endoplasmic reticulum stress
- nk cells
- stem cells
- cell death
- cell surface
- mesenchymal stem cells
- newly diagnosed
- cell therapy
- working memory
- chronic kidney disease
- pi k akt
- peritoneal dialysis
- prognostic factors
- combination therapy
- patient reported
- smoking cessation
- cancer therapy
- replacement therapy