Werner Juwita, Lee Alex G, Zhang Chujing, Abelson Sydney, Xirenayi Sherin, Rivera Jose, Yousuf Khadija, Shin Hanna, Patiño-Escobar Bonell, Bachl Stefanie, Mandal Kamal, Barpanda Abhilash, Ramos Emilio, Izgutdina Adila, Chaudhuri Sibapriya, Temple William C, Bhatnagar Shubhmita, Dardis Jackson K, Meyer Julia, Morales Carolina, Meshinchi Soheil, Loh Mignon L, Braun Benjamin, Tasian Sarah K, Wiita Arun P, Stieglitz Elliot
Department of Pediatrics, Benioff Children's Hospitals, University of California, San Francisco, CA, USA.
Department of Pediatric Hematology and Oncology and Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany.
Nat Commun. 2025 Apr 23;16(1):3804. doi: 10.1038/s41467-025-59040-6.
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.
青少年骨髓单核细胞白血病（JMML）是一种主要影响婴幼儿的骨髓增殖性疾病。造血干细胞移植（HSCT）是标准治疗方法，但HSCT后复发很常见，这凸显了创新疗法的必要性。虽然嵌合抗原受体（CAR）T细胞过继性免疫疗法改善了晚期淋巴系统恶性肿瘤患者的治疗效果，但尚未在JMML中进行全面评估。在本研究中，我们使用批量和单细胞RNA测序、质谱分析和流式细胞术来鉴定JMML患者细胞表面CLL-1（由CLEC12A编码）的过表达。我们开发了用于临床前测试的CLL-1 CAR T细胞免疫疗法（CLL1CART），并报告了其体外和体内的抗白血病活性。值得注意的是，CLL1CART减少了体内白血病干细胞的数量和连续移植能力。这些临床前数据支持在复发/难治性JMML儿童中开展靶向CLL-1免疫疗法的研发和临床研究。
Zotero 插件
