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Cellular immunotherapy targeting CLL-1 for juvenile myelomonocytic leukemia

Author

Listed:
  • Juwita Werner

    (University of California
    Hannover Medical School)

  • Alex G. Lee

    (University of California)

  • Chujing Zhang

    (University of California)

  • Sydney Abelson

    (University of California)

  • Sherin Xirenayi

    (University of California)

  • Jose Rivera

    (University of California)

  • Khadija Yousuf

    (University of California)

  • Hanna Shin

    (University of California)

  • Bonell Patiño-Escobar

    (University of California)

  • Stefanie Bachl

    (University of California
    Gladstone-UCSF Institute of Genomic Immunology)

  • Kamal Mandal

    (University of California
    Gujarat Biotechnology University)

  • Abhilash Barpanda

    (University of California)

  • Emilio Ramos

    (University of California)

  • Adila Izgutdina

    (University of California)

  • Sibapriya Chaudhuri

    (University of California)

  • William C. Temple

    (University of California
    University of California)

  • Shubhmita Bhatnagar

    (Children’s Hospital of Philadelphia)

  • Jackson K. Dardis

    (Children’s Hospital of Philadelphia)

  • Julia Meyer

    (University of California)

  • Carolina Morales

    (University of California)

  • Soheil Meshinchi

    (Fred Hutchinson Cancer Center)

  • Mignon L. Loh

    (University of Washington)

  • Benjamin Braun

    (University of California)

  • Sarah K. Tasian

    (Children’s Hospital of Philadelphia
    University of Pennsylvania School of Medicine)

  • Arun P. Wiita

    (University of California
    University of California
    Chan Zuckerberg Biohub San Francisco
    Parker Institute for Cancer Immunotherapy)

  • Elliot Stieglitz

    (University of California)

Abstract

Juvenile myelomonocytic leukemia (JMML) is a myeloproliferative disorder that predominantly affects infants and young children. Hematopoietic stem cell transplantation (HSCT) is standard of care, but post-HSCT relapse is common, highlighting the need for innovative therapies. While adoptive immunotherapy with chimeric antigen receptor (CAR) T cells has improved outcomes for patients with advanced lymphoid malignancies, it has not been comprehensively evaluated in JMML. In the present study, we use bulk and single-cell RNA sequencing, mass spectrometry, and flow cytometry to identify overexpression of CLL-1 (encoded by CLEC12A) on the cell surface of cells from patients with JMML. We develop immunotherapy with CLL-1 CAR T cells (CLL1CART) for preclinical testing and report in vitro and in vivo anti-leukemia activity. Notably, CLL1CART reduce the number of leukemic stem cells and serial transplantability in vivo. These preclinical data support the development and clinical investigation of CLL-1-targeting immunotherapy in children with relapsed/refractory JMML.

Suggested Citation

  • Juwita Werner & Alex G. Lee & Chujing Zhang & Sydney Abelson & Sherin Xirenayi & Jose Rivera & Khadija Yousuf & Hanna Shin & Bonell Patiño-Escobar & Stefanie Bachl & Kamal Mandal & Abhilash Barpanda &, 2025. "Cellular immunotherapy targeting CLL-1 for juvenile myelomonocytic leukemia," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59040-6
    DOI: 10.1038/s41467-025-59040-6
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