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September 23, 2020 /--- -- A new study has found CD19 molecules in brain cells that protect the blood-brain barrier (BBB).
well known, CD19 is a star target in CAR-T cell immunotherapy, widely expressed in leukemia, lymphoma and multiple myeloma cells.
led by Dr. Avery Posey, assistant professor of systems pharmacology and translational therapy at the Perelman School of Medicine, found that this may be the cause of neurotoxicity in patients receiving CD19 CAR T cell immunotherapy.
results were published in cell.
Our study shows that CD19 expression is present in some non-B cells, which may be related to neurotoxicity that we observed in patients treated with CD19-targeted CAR T cell therapy," said
Posey.
Refore, can we identify a better target to eliminate B-cell-related malignancies other than CD19, or can we engineer and optimize CART cells around cd19 expression of this brain cell.
" team observed that when CAR T cells were targeted into mice, the permeability of the blood-brain barrier increased even if the mice lacked B-cells, but there was no significant change in the permeability of the blood-brain barrier when human CD19 was used as a control therapy (mice did not express human CD19).
the higher risk of neurotoxicity in CD19 immunotherapy than in treatments for other B-cell proteins, such as CD20, the study highlights the importance of finding any cell subplogies other than B-cells that potentially express CD19 molecules.
(Photo Source: www.pixabay.com) also highlights the potential uses of developing comprehensive human single-cell maps for clinical medicine.
sequencing is an unbiased, gene-wide measurement of gene expression and even captures rare cell populations.
these rare cell types may not be missed from measurements of large tissues due to their low frequency, but as this study shows, it may be important to understand the clinical effects of targeted therapy.
current CAR T cells can only identify individual antigens, the next generation of CAR T cells may be able to distinguish between unique combinations of target antigens, improving their cell type specificity.
researchers predict that a comprehensive gene expression database covering all human cell types will be able to accurately identify cell type-specific target antigens that can be used to design safe and effective cell immunotherapy.
(bioon.com) Source: Researchers discover potential cause of immunotherapy-neurotoxicity Source: Kevin R. Parker et al. Single-Cell Analytics Identify Brain Mural Cells ExpressING CD19 as Off Potential-Tumor Targets for CAR-T Immunotherapies. Cell. Published: September 21, 2020. DOI: doi.org/10.1016/j.cell.2020.08.022.