Super-resolution microscopy reveals ultra-low CD19 expression on myeloma cells that triggers elimination by CD19 CAR-T
Please always quote using this URN: urn:nbn:de:bvb:20-opus-232258
- 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 10Immunotherapy 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.…
Author: | Thomas Nerreter, Sebastian Letschert, Ralph Götz, Sören Doose, Sophia Danhof, Hermann Einsele, Markus Sauer, Michael Hudecek |
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URN: | urn:nbn:de:bvb:20-opus-232258 |
Document Type: | Journal article |
Faculties: | Medizinische Fakultät / Medizinische Klinik und Poliklinik II |
Fakultät für Biologie / Theodor-Boveri-Institut für Biowissenschaften | |
Language: | English |
Parent Title (English): | Nature Communications |
Year of Completion: | 2019 |
Volume: | 10 |
Article Number: | 3137 |
Source: | Nature Communications (2019) 10:3137. https://doi.org/10.1038/s41467-019-10948-w |
DOI: | https://doi.org/10.1038/s41467-019-10948-w |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit | |
Tag: | cancer imaging; cancer immunotherapy; imaging |
Release Date: | 2024/07/18 |
OpenAIRE: | OpenAIRE |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |