Cellular immunotherapy targeting CLL-1 for juvenile myelomonocytic leukemia
Abstract
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.
Article Details
Authors (26)
Juwita Werner
Alex G. Lee
Chujing Zhang
Sydney Abelson
Sherin Xirenayi
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
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
Seattle Children’s Hospital, Seattle
Benjamin Braun
Sarah K. Tasian
Arun P. Wiita
Elliot Stieglitz