CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Mouse models of diffuse large B cell lymphoma.
Mouse models of diffuse large B cell lymphoma.
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弥漫大B细胞淋巴瘤(DLBCL)是一种遗传异质性极高的疾病。然而,迄今绝大多数患者仍接受标准化的一线化学免疫治疗方案,通常以蒽环类药物为基础。采用这些方案后,约65%的患者可治愈,其余35%将出现复发/难治性疾病;即使在CAR-T 细胞时代,这类疾病仍难以治疗。为系统应对这一重大医疗需求,设计、建立并应用合适的体内模型系统十分重要,使其能够再现疾病生物学特征、异质性及药物应答。近期发表的大规模综合基因组特征研究已确定DLBCL分子亚组,为建立自发性小鼠模型提供了理想框架,也可作为细胞系来源或患者来源DLBCL小鼠模型的理想基准。本文讨论人DLBCL小鼠建模领域当前的先进研究,特别关注疾病生物学、遗传学定义的分子脆弱性及潜在靶向策略。
Diffuse large B cell lymphoma (DLBCL) is a genetically highly heterogeneous disease. Yet, to date, the vast majority of patients receive standardized frontline chemo-immune-therapy consisting of an anthracycline backbone. Using these regimens, approximately 65% of patients can be cured, whereas the remaining 35% of patients will face relapsed or refractory disease, which, even in the era of CAR-T cells, is difficult to treat.
To systematically tackle this high medical need, it is important to design, generate and deploy suitable in vivo model systems that capture disease biology, heterogeneity and drug response. Recently published, large comprehensive genomic characterization studies, which defined molecular sub-groups of DLBCL, provide an ideal framework for the generation of autochthonous mouse models, as well as an ideal benchmark for cell line-derived or patient-derived mouse models of DLBCL.
Here we discuss the current state of the art in the field of mouse modelling of human DLBCL, with a particular focus on disease biology and genetically defined molecular vulnerabilities, as well as potential targeting strategies.
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