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.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Metabolic vulnerabilities and therapeutic opportunities in diffuse large B-cell lymphoma.
Metabolic vulnerabilities and therapeutic opportunities in diffuse large B-cell lymphoma.
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弥漫性大 B 细胞淋巴瘤(DLBCL)是最常见的非霍奇金淋巴瘤(NHL),具有显著生物学异质性。传统分类主要依据遗传和转录组特征,而新证据提示存在可能带来新治疗弱点的代谢亚型。有趣的是,目前的化学免疫治疗方案会对肿瘤代谢产生强烈但非特异性影响,虽可意外利用代谢依赖性,却缺乏精准性。靶向葡萄糖、氨基酸、脂质和线粒体代谢的新型抑制剂,可对按代谢特征划分的淋巴瘤亚群产生选择性细胞毒作用。本综述探讨标准疗法如何利用 DLBCL 代谢,考察不同亚型间的异质性,并评估靶向代谢治疗。文章还讨论与现有治疗方案和免疫治疗联合的新兴策略,尤其关注肿瘤细胞与免疫效应细胞(包括 CAR-T 细胞和双特异性抗体)之间的代谢相互作用。作者强调,需要开展转化研究,通过代谢组学分析验证代谢亚型、识别预测性生物标志物并开发合理联合方案。摆脱经验性治疗、转向有策略的代谢靶向,为改善这种侵袭性且多样化淋巴瘤患者的结局提供机遇。
Diffuse large B cell lymphoma (DLBCL), the most common type of non-Hodgkin lymphoma (NHL), exhibits considerable biological heterogeneity. While its classification has traditionally relied on genetic and transcriptomic features, emerging evidence points to distinct metabolic subtypes that may represent novel therapeutic vulnerabilities.
Intriguingly, current chemoimmunotherapy regimens exert profound but non-specific effects on tumour metabolism, inadvertently exploiting metabolic dependencies yet without precision. Novel inhibitors targeting glucose, amino acid, lipid, and mitochondrial metabolism demonstrate selective cytotoxicity in metabolically defined lymphoma subsets. This review investigates how standard therapies exploit DLBCL metabolism and examines heterogeneity across subtypes, and evaluates targeted metabolic therapies.
We discuss emerging combination strategies with current therapeutic regimes and immunotherapy. Particular focus is given to the metabolic interactions between tumour cells and immune effectors, including CAR T cells and bispecific antibodies.
We highlight the importance of translational research to validate metabolic subtypes through metabolomic profiling, identify predictive biomarkers, and develop rational combinations. Moving beyond empiric therapy towards strategic metabolic targeting offers an opportunity to enhance outcomes for patients with this aggressive and diverse lymphoma.
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