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

Author

Listed:
  • 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)

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

Suggested Citation

  • Thomas Nerreter & Sebastian Letschert & Ralph Götz & Sören Doose & Sophia Danhof & Hermann Einsele & Markus Sauer & Michael Hudecek, 2019. "Super-resolution microscopy reveals ultra-low CD19 expression on myeloma cells that triggers elimination by CD19 CAR-T," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10948-w
    DOI: 10.1038/s41467-019-10948-w
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    Cited by:

    1. Markus Haake & Beatrice Haack & Tina Schäfer & Patrick N. Harter & Greta Mattavelli & Patrick Eiring & Neha Vashist & Florian Wedekink & Sabrina Genssler & Birgitt Fischer & Julia Dahlhoff & Fatemeh M, 2023. "Tumor-derived GDF-15 blocks LFA-1 dependent T cell recruitment and suppresses responses to anti-PD-1 treatment," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Jonathan Schubert & Andrea Schulze & Chrisostomos Prodromou & Hannes Neuweiler, 2021. "Two-colour single-molecule photoinduced electron transfer fluorescence imaging microscopy of chaperone dynamics," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    3. Rebecca Boiarsky & Nicholas J. Haradhvala & Jean-Baptiste Alberge & Romanos Sklavenitis-Pistofidis & Tarek H. Mouhieddine & Oksana Zavidij & Ming-Chieh Shih & Danielle Firer & Mendy Miller & Habib El-, 2022. "Single cell characterization of myeloma and its precursor conditions reveals transcriptional signatures of early tumorigenesis," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    4. Ming Shi & Jiaojiao Wang & Hongming Huang & Dan Liu & Hai Cheng & Xu Wang & Wei Chen & Zhiling Yan & Wei Sang & Kunming Qi & Depeng Li & Feng Zhu & Zhenyu Li & Jianlin Qiao & Qingyun Wu & Lingyu Zeng , 2024. "Bispecific CAR T cell therapy targeting BCMA and CD19 in relapsed/refractory multiple myeloma: a phase I/II trial," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    5. Nina E. Weisser & Mario Sanches & Eric Escobar-Cabrera & Jason O’Toole & Elizabeth Whalen & Peter W. Y. Chan & Grant Wickman & Libin Abraham & Kate Choi & Bryant Harbourne & Antonios Samiotakis & Andr, 2023. "An anti-HER2 biparatopic antibody that induces unique HER2 clustering and complement-dependent cytotoxicity," Nature Communications, Nature, vol. 14(1), pages 1-22, December.

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