TY  - JOUR
A1  - Nerreter, Thomas
A1  - Letschert, Sebastian
A1  - Götz, Ralph
A1  - Doose, Sören
A1  - Danhof, Sophia
A1  - Einsele, Hermann
A1  - Sauer, Markus
A1  - Hudecek, Michael
T1  - Super-resolution microscopy reveals ultra-low CD19 expression on myeloma cells that triggers elimination by CD19 CAR-T
T2  - Nature Communications
N2  - 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.
KW  - cancer imaging
KW  - cancer immunotherapy
KW  - imaging
Y1  - 2019
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/23225
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-232258
VL  - 10
ER  -