Research Highlights: Treatment for White Blood Cell Malignancies Causes Nervous System Toxicity

Original Article: https://doi.org/10.1016/j.cell.2020.08.022

  • The human CD19 antigen is a transmembrane glycoprotein belonging to the immunoglobulin superfamily.
  • CD19 is critically involved in establishing intrinsic B cell signaling thresholds through modulating both B cell receptor-dependent and independent signaling.
  • CD19-directed immunotherapies are clinically effective for treating B cell malignancies but also cause a high incidence of neurotoxicity.
  • A group of patients treated with chimeric antigen receptor T cells or bispecific T cell engager antibodies display severe neurotoxicity.
  • The neurotoxicity includes fatal brain edema associated with T cell infiltration into the brain.
  • The study reports that mural cells, surrounding the endothelium, express CD19.
  • Endothelial cells are critical for blood-brain-barrier integrity.
  • Researchers identify CD19 expression in brain mural cells using single-cell RNA sequencing data and confirm blood vessel 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.
  • Data suggest an on-target mechanism for neurotoxicity in CD19-directed therapies and highlight the utility of human single-cell atlases for designing immunotherapies.

Source:

https://doi.org/10.1016/j.cell.2020.08.022

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3520838/


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