Super-resolution microscopy reveals ultra-low CD19 expression on myeloma cells that triggers elimination by CD19 CAR-T

Thomas Nerreter, Sebastian Letschert, Ralph Götz, Sören Doose, Sophia Danhof, Hermann Einsele, Markus Sauer () and Michael Hudecek ()
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Thomas Nerreter: Universitätsklinikum Würzburg
Sebastian Letschert: Biocenter, Julius Maximilian University Würzburg, Am Hubland
Ralph Götz: Biocenter, Julius Maximilian University Würzburg, Am Hubland
Sören Doose: Biocenter, Julius Maximilian University Würzburg, Am Hubland
Sophia Danhof: Universitätsklinikum Würzburg
Hermann Einsele: Universitätsklinikum Würzburg
Markus Sauer: Biocenter, Julius Maximilian University Würzburg, Am Hubland
Michael Hudecek: Universitätsklinikum Würzburg

Nature Communications, 2019, vol. 10, issue 1, 1-11

Abstract: Abstract Immunotherapy with chimeric antigen receptor-engineered T-cells (CAR-T) is under investigation in multiple myeloma. There are reports of myeloma remission after CD19 CAR-T therapy, although CD19 is hardly detectable on myeloma cells by flow cytometry (FC). We apply single molecule-sensitive direct stochastic optical reconstruction microscopy (dSTORM), and demonstrate CD19 expression on a fraction of myeloma cells (10.3–80%) in 10 out of 14 patients (density: 13–5,000 molecules per cell). In contrast, FC detects CD19 in only 2 of these 10 patients, on a smaller fraction of cells. Treatment with CD19 CAR-T in vitro results in elimination of CD19-positive myeloma cells, including those with

Date: 2019
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DOI: 10.1038/s41467-019-10948-w

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