Journal
NATURE COMMUNICATIONS
Volume 11, Issue 1, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-020-14619-z
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Funding
- International Myeloma Foundation Senior Grant
- American Association for Cancer Research (AACR) fellowship
- NCCN Young Investigator Award
- Huntsman Cancer Institute Experimental Therapeutics program - National Cancer Institute of the National Institutes of Health [P30CA042014]
- DOD Era of Hope Scholar Expansion Award [W81XWH-12-1-0077]
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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.
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