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复发/难治性套细胞淋巴瘤靶向治疗与细胞治疗进展:免疫治疗策略与挑战

英文原题:Advances in targeted and cellular therapies for relapsed/refractory mantle cell lymphoma: immunotherapeutic strategies and challenges.

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Advances in targeted and cellular therapies for relapsed/refractory mantle cell lymphoma: immunotherapeutic strategies and challenges.

PubMed 2026/06/24(内容时间) Clin Transl Oncol Q3 · IF 2.7(JCR 2025)

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中文摘要

套细胞淋巴瘤是一种侵袭性、异质性B细胞恶性肿瘤,具有频繁复发、治疗耐药及晚期长期生存率低等特点。靶向治疗、细胞免疫治疗及分子分型的近期进展改变了该病的管理。本综述总结新兴治疗策略、耐药机制和转化研究方法,重点关注布鲁顿酪氨酸激酶(BTK)抑制剂、CAR-T 细胞疗法、双特异性抗体、靶向SOX11治疗、维奈克拉方案及精准医疗。

我们开展综合性叙述综述,分析近期临床前研究、临床试验、转化研究及真实世界治疗和耐药生物学证据,重点关注靶向治疗、免疫治疗、分子生物标志物及细胞工程。治疗进展改善了复发/难治性疾病结局:共价及非共价BTK抑制剂、CAR-T、双特异性抗体及维奈克拉联合方案均显示显著抗肿瘤活性。

然而,克隆演化、抗原逃逸、肿瘤微环境重塑及耐药持存细胞驱动的耐药限制了缓解持久性。靶向SOX11的策略、基因编辑技术及微小残留病监测具有转化前景。分子分型和免疫疗法正在重塑个体化管理。联合治疗及生物标志物指导的患者选择可能克服耐药并改善生存,但治疗毒性、可及性有限和成本高仍构成挑战。靶向疗法和细胞疗法正在重新定义治疗模式;精准医疗、耐药导向策略及免疫治疗联合有望改善长期控制。本综述整合了耐药生物学、SOX11治疗、CAR-T 失败机制及精准策略方面的证据。未来研究应优先考虑生物标志物指导方法、优化CAR-T、更安全的药物及可及性更高的难治病例治疗方案。

展开英文摘要原文

Mantle cell lymphoma is an aggressive, heterogeneous B-cell malignancy characterized by frequent relapse, therapeutic resistance, and poor long-term survival in advanced disease. Recent advances in targeted therapy, cellular immunotherapy, and molecular profiling have transformed management. This review summarizes emerging strategies, resistance mechanisms, and translational approaches, emphasizing Bruton tyrosine kinase (BTK) inhibitors, CAR T-cell therapy, bispecific antibodies, SOX11-directed therapy, venetoclax regimens, and precision medicine.

A comprehensive narrative review analyzed recent preclinical studies, clinical trials, translational research, and real-world evidence on treatment and resistance biology, focusing on targeted therapies, immunotherapy, molecular biomarkers, and cellular engineering. Therapeutic advances have improved outcomes in relapsed/refractory disease: covalent and noncovalent BTK inhibitors, CAR T-cell therapy, bispecific antibodies, and venetoclax combinations demonstrate significant antitumor activity.

However, resistance driven by clonal evolution, antigen escape, tumor microenvironment remodeling, and drug-tolerant persister cells limits durable remission. SOX11-targeted approaches, gene-editing technologies, and measurable residual disease monitoring offer translational promise. Molecular profiling and immunotherapeutics are reshaping personalized management. Combination therapies and biomarker-guided selection may overcome resistance and enhance survival, though treatment toxicity, limited accessibility, and high costs pose challenges.

Targeted and cellular therapies are redefining paradigms; precision medicine, resistance-directed strategies, and immunotherapeutic combinations could improve long-term control. This review uniquely integrates evidence on resistance biology, SOX11 therapy, CAR T-cell failure mechanisms, and precision strategies. Future studies should prioritize biomarker-driven approaches, CAR T-cell optimization, safer agents, and accessible treatments for refractory cases.

论文信息

作者
Sivalingam AM
单位
Natural Products and Nanobiotechnology Research Lab, Saveetha Institute of Basic Medical Sciences (SIBMS), Saveetha Institute of Medical and Technical Sciences (SIMATS), (Saveetha University), Thandalam, Chennai, Tamil Nadu, 602105, India. mathavan062@gmail.com.India
文献类型
综述
期刊
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico2026 Jun 24
原文标识
PubMed 42340653 · DOI 10.1007/s12094-026-04474-7