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<p>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 <i>CLEC12A</i>) on the cell surface of cells from patients with JMML. We develop immunotherapy with&#xa0;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.</p>

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Cellular immunotherapy targeting CLL-1 for juvenile myelomonocytic leukemia

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月23日

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  • 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,
  • Emilio Ramos,
  • Adila Izgutdina,
  • Sibapriya Chaudhuri,
  • William C. Temple,
  • Shubhmita Bhatnagar,
  • Jackson K. Dardis,
  • Julia Meyer,
  • Carolina Morales,
  • Soheil Meshinchi,
  • Mignon L. Loh,
  • Benjamin Braun,
  • Sarah K. Tasian,
  • Arun P. Wiita,
  • Elliot Stieglitz

摘要

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.