抗 CD22/CD19 CAR-T 细胞疗法 CART2219.1 在成人和儿童复发/难治性 B-ALL 中的 I/II 期试验
A Phase I/II Trial of Anti-CD22/CD19 CAR-T Cell Therapy, CART2219.1, in Adult and Pediatric Relapsed/Refractory B-ALL.
在一项多中心I/II期试验中,所有患者(n=11;7名儿童,4名成人)在第28天均达到完全缓解(91%为微小残留病阴性)。
英文原题:Dynamic evolution of bone marrow adipocyte in B cell acute lymphoblastic leukemia: insights from diagnosis to post-chemotherapy.
我们的发现为进一步深入理解BMM与B-ALL之间的动态平衡提供了新的视角。
脂肪细胞是骨髓微环境(BMM)中一种独特且多功能的组成部分。然而,从B细胞急性淋巴细胞白血病(B-ALL)诊断到治疗后状态,骨髓(BM)脂肪细胞的动态演变及其如何影响白血病进展,仍未被充分阐明。本研究采用了原代患者来源异种移植模型(PDXs)和基质细胞共培养系统。我们发现,从B-ALL初诊到化疗后阶段,BM脂肪细胞呈现动态演变,从初始白血病微环境中的细胞耗竭状态转变为缓解后的完全恢复状态。BM脂肪细胞增加会延缓PDX模型中B-ALL细胞的植入,并在体外抑制B-ALL细胞生长。在机制上,脂肪细胞富集微环境中B-ALL细胞的增殖停滞,可能归因于脂肪细胞自身分泌的脂联素的存在以及间充质干细胞(MSCs)分泌的细胞因子的缺失。总之,我们的发现为进一步深入理解BMM与B-ALL之间的动态平衡提供了新的视角。
Adipocyte is a unique and versatile component of bone marrow microenvironment (BMM). However, the dynamic evolution of Bone Marrow (BM) adipocytes from the diagnosis of B cell Acute Lymphoblastic Leukemia (B-ALL) to the post-treatment state, and how they affect the progression of leukemia, remains inadequately explicated. Primary patient-derived xenograft models (PDXs) and stromal cell co-culture system are employed in this study. We show that the dynamic evolution of BM adipocytes from initial diagnosis of B-ALL to the post-chemotherapy phase, transitioning from cellular depletion in the initial leukemia niche to a fully restored state upon remission. Increased BM adipocytes retards engraftment of B-ALL cells in PDX models and inhibits cells growth of B-ALL in vitro. Mechanistically, the proliferation arrest of B-ALL cells in the context of adipocytes-enrichment niche, might attribute to the presence of adiponectin secreted by adipocytes themselves and the absence of cytokines secreted by mesenchymal stem cell (MSCs). In summary, our findings offer a novel perspective for further in-depth understanding of the dynamic balance between BMM and B-ALL.
MEMBER ACCOUNT
登录成功会直接打开下一页。