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:Frontline Therapy in Diffuse Large B-Cell Lymphoma: Evolving Standards, Biological Insights, and Future Directions.
Frontline Therapy in Diffuse Large B-Cell Lymphoma: Evolving Standards, Biological Insights, and Future Directions.
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弥漫性大B细胞淋巴瘤(DLBCL)仍是最常见的侵袭性淋巴瘤,具有显著的生物学异质性和多样的临床表现。二十多年来,R-CHOP一直是一线治疗基石,可治愈约三分之二患者。尽管如此,相当一部分患者,尤其是具有高危生物学特征、双打击遗传学特征、活化B细胞样(ABC)亚型或不良临床特征者,仍会复发或出现难治性疾病。淋巴瘤生物学、免疫治疗和靶向治疗的近期进展,推动了改善一线疗效的广泛探索。相关策略包括优化细胞毒性药物基础方案、加入抗体药物偶联物(ADC)、免疫调节药物(IMiD)及双特异性抗体,并探索一线CAR-T 细胞治疗的可行性。本综述系统梳理了塑造当代一线治疗的生物学依据、临床证据、试验结果和实践考量,重点介绍分子分型、肿瘤微环境及高危生物标志物的新兴作用,并讨论将新疗法纳入标准治疗的挑战与机遇。尽管R-CHOP仍是通用基础方案,治疗格局正进入变革时期;基于泊洛妥珠单抗的方案、双特异性联合方案和精准指导策略,有望重新定义部分患者亚群的一线治疗。
Diffuse large B-cell lymphoma (DLBCL) remains the most common aggressive lymphoma, representing a biologically heterogeneous disease with diverse clinical behaviors. For more than two decades, R-CHOP has been the cornerstone of frontline treatment, curing approximately two-thirds of patients. Despite this success, a substantial subset-particularly those with high-risk biology, double-hit genetics, activated B-cell-like (ABC) subtype, or adverse clinical features-still experience relapse or refractory disease.
Recent advances in lymphoma biology, immunotherapy, and targeted therapy have stimulated intense interest in improving frontline outcomes. Strategies include optimizing cytotoxic backbone regimens, incorporating antibody-drug conjugates (ADCs), immunomodulatory agents (IMiDs), bispecific antibodies, and exploring the feasibility of frontline CAR-T cell therapy. This review provides a comprehensive and discursive synthesis of the biological rationale, clinical evidence, trial results, and practical considerations shaping contemporary frontline treatment.
We highlight the emerging role of molecular subtyping, the tumor microenvironment, and high-risk biomarkers, while discussing ongoing challenges and opportunities in integrating novel modalities into standard practice. Although R-CHOP remains the universal backbone, the therapeutic landscape is entering a transformative era, with polatuzumab-based regimens, bispecific combinations, and precision-guided approaches positioned to redefine frontline care for selected subgroups.
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