CD229 CAR T cells eliminate multiple myeloma and tumor propagating cells without fratricide
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 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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 07, 2020
- Source ID
- 10.1038/s41467-020-14619-z
Entities
People
- Alana L Welm
- Djordje Atanackovic
- Erica R. Vander Mause
- Jens Panse
- K. David Li
- Michael Olson
- Patricia Davis
- Rodney R. Miles
- Sabarinath V. Radhakrishnan
- Sandra D. Scherer
- Sara Yousef
- Tim Luetkens
- William Matsui
- Yasmina Abdiche
Organizations
- American Association for Cancer Research
- Division of Cancer Epidemiology and Genetics, National Cancer Institute
- National Cancer Institute
- National Comprehensive Cancer Network
- United States Department of Defense