Cellular immunotherapy targeting CLL-1 for juvenile myelomonocytic leukemia

Cellular immunotherapy targeting CLL-1 for juvenile myelomonocytic leukemia

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...

Full description

Saved in:
Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-59040-6
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2041-1723

Similar Items