肿瘤细胞治疗研究
英文原题：Cellular immunotherapy targeting CLL-1 for juvenile myelomonocytic leukemia.
幼年型粒单核细胞白血病（JMML）是一种主要累及婴幼儿的骨髓增殖性疾病。
幼年型粒单核细胞白血病（JMML）是一种主要影响婴幼儿及低龄儿童的骨髓增殖性疾病。造血干细胞移植（HSCT）是标准治疗，但移植后常复发，凸显了创新疗法的必要性。嵌合抗原受体（CAR）T细胞过继免疫疗法改善了晚期淋巴系统恶性肿瘤患者的结局，但尚未在JMML中得到全面评估。本研究结合整体及单细胞RNA测序、质谱和流式细胞术，发现JMML患者细胞表面CLL-1（由CLEC12A编码）过表达。研究者开发靶向CLL-1的CAR-T免疫疗法（CLL1CART）用于临床前测试，并报告其体内外抗白血病活性。值得注意的是，CLL1CART可减少体内白血病干细胞数量及其连续移植能力。这些临床前数据支持开发靶向CLL-1的免疫疗法，并在复发/难治性JMML儿童中开展临床研究。
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.
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