CD229 CAR T cells eliminate multiple myeloma and tumor propagating cells without fratricide. Nat Commun 2020 Feb 07;11(1):798
Date
02/09/2020Pubmed ID
32034142Pubmed Central ID
PMC7005855DOI
10.1038/s41467-020-14619-zScopus ID
2-s2.0-85079080842 (requires institutional sign-in at Scopus site) 41 CitationsAbstract
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 TÂ 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.
Author List
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 DAuthor
Sabarinath Venniyil Radhakrishnan MD Assistant Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAntibodies
B-Lymphocytes
Humans
Immunotherapy, Adoptive
K562 Cells
Male
Mice, Inbred NOD
Multiple Myeloma
Receptors, Antigen, T-Cell
Signaling Lymphocytic Activation Molecule Family
T-Lymphocytes
Xenograft Model Antitumor Assays
