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:Single-cell transcriptomic analysis of the immune microenvironment in pediatric acute leukemia.
复发和治疗耐药是儿童B细胞急性淋巴细胞白血病(B-ALL)和急性髓系白血病(AML)管理中面临的重大挑战。
复发和治疗耐药是儿童B细胞急性淋巴细胞白血病(B-ALL)和急性髓系白血病(AML)管理中面临的重大挑战。由于免疫抑制性肿瘤微环境(TME)和缺乏合适的免疫治疗靶点等因素,免疫治疗在白血病中的疗效仍然有限。因此,有必要深入表征儿童白血病的TME以提高免疫治疗的疗效。在此,我们使用单细胞RNA测序(scRNA-seq)来表征儿童B-ALL和AML的TME,特别关注骨髓来源的T细胞。此外,我们研究了儿童AML在起始、缓解和复发阶段的转录组变化。我们的发现揭示了特定的功能表达程序与各种T细胞亚群的波动相关,这可能与AML进展和复发有关。此外,我们对细胞通讯网络的分析确定了VISTA、CD244和TIM3作为儿童AML的潜在免疫治疗靶点。最后,我们在诊断为B-ALL和AML的儿童患者样本中检测到γδ T细胞及相关功能基因比例升高,这可能为开发新的治疗方法提供信息,潜在聚焦于γδ T细胞。
Relapse and treatment resistance pose significant challenges in the management of pediatric B cell acute lymphoblastic leukemia (B-ALL) and acute myeloid leukemia (AML). The efficacy of immunotherapy in leukemia remains limited due to factors such as the immunosuppressive tumor microenvironment (TME) and lack of suitable immunotherapeutic targets. Thus, an in-depth characterization of the TME in pediatric leukemia is warranted to improve the efficacy of immunotherapy. Here, we used single-cell RNA sequencing (scRNA-seq) to characterize the TME of pediatric B-ALL and AML, focusing specifically on bone-marrow-derived T cells. Moreover, we investigated the transcriptome changes during the initiation, remission, and relapse stages of pediatric AML. Our findings revealed that specific functional expression programs correlated with fluctuations in various T cell subsets, which may be associated with AML progression and relapse. Furthermore, our analysis of cellular communication networks led to the identification of VISTA, CD244, and TIM3 as potential immunotherapeutic targets in pediatric AML. Finally, we detected elevated proportions of γδ T cells and associated functional genes in samples from pediatric patients diagnosed with B-ALL and AML, which could inform the development of novel therapeutic approaches, potentially focusing on γδ T cells.
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