Journal
CELL
Volume 183, Issue 1, Pages 126-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2020.08.022
Keywords
-
Categories
Funding
- National Institutes of Health (NIH) [P50-HG007735, P50-NS062684, K08CA230188, U01MH105989, P41-EB015893]
- Department of Veterans Affairs [IK2BX004183]
- Parker Institute for Cancer Immunotherapy
- Scleroderma Research Foundation
- Private Foundation of the Geneva University Hospital, Switzerland
- Stanford Graduate Fellowship
- Parker Bridge Scholar Award from the Parker Institute for Cancer Immunotherapy
- Cancer Research Institute
- Burroughs Wellcome Fund
Ask authors/readers for more resources
CD19-directed immunotherapies are clinically effective for treating B cell malignancies but also cause a high incidence of neurotoxicity. A subset of patients treated with chimeric antigen receptor (CAR) T cells or bispecific T cell engager (BiTE) antibodies display severe neurotoxicity, including fatal cerebral edema associated with T cell infiltration into the brain. Here, we report that mural cells, which surround the endothelium and are critical for blood-brain-barrier integrity, express CD19. We identify CD19 expression in brain mural cells using single-cell RNA sequencing data and confirm perivascular staining at the protein level. CD19 expression in the brain begins early in development alongside the emergence of mural cell lineages and persists throughout adulthood across brain regions. Mouse mural cells demonstrate lower levels of Cd19 expression, suggesting limitations in preclinical animal models of neurotoxicity. These data suggest an on-target mechanism for neurotoxicity in CD19-directed therapies and highlight the utility of human single-cell atlases for designing immunotherapies.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available