Super-resolution microscopy reveals ultra-low CD19 expression on myeloma cells that triggers elimination by CD19 CAR-T
Nerreter T, Letschert S, Goetz R, Doose S, Danhof S, Einsele H, Sauer M, Hudecek M (2019)
Publication Type: Journal article
Publication year: 2019
Journal
Book Volume: 10
Article Number: 3137
Journal Issue: 1
DOI: 10.1038/s41467-019-10948-w
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 <100 CD19 molecules per cell. Similar data are obtained by dSTORM analyses of CD20 expression on myeloma cells and CD20 CAR-T. These data establish a sensitivity threshold for CAR-T and illustrate how super-resolution microscopy can guide patient selection in immunotherapy to exploit ultra-low density antigens.
Involved external institutions
Germany (DE)How to cite
APA:
Nerreter, T., Letschert, S., Goetz, R., Doose, S., Danhof, S., Einsele, H.,... Hudecek, M. (2019). Super-resolution microscopy reveals ultra-low CD19 expression on myeloma cells that triggers elimination by CD19 CAR-T. Nature Communications, 10(1). https://doi.org/10.1038/s41467-019-10948-w
MLA:
Nerreter, Thomas, et al. "Super-resolution microscopy reveals ultra-low CD19 expression on myeloma cells that triggers elimination by CD19 CAR-T." Nature Communications 10.1 (2019).
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