CD81 通过阻断 CD274/PD-L1 的选择性自噬降解驱动放射抵抗性胶质母细胞瘤的免疫逃逸
CD81 drives immune evasion in radioresistant glioblastoma by blocking selective autophagic degradation of CD274/PD-L1.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Antibody therapies in glioblastoma: Overcoming micro-environmental barriers.
Antibody therapies in glioblastoma: Overcoming micro-environmental barriers.
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胶质母细胞瘤(GBM)仍然是成人中最具侵袭性的脑肿瘤,二十年来中位生存期基本未变。基于抗体的疗法在血液系统肿瘤和全身性肿瘤中已显示出前景,但其向 GBM 的转化受到肿瘤恶劣微环境和免疫逃逸机制的阻碍。在 PubMed、Scopus、Web of Science 和 ClinicalTrials.gov 中对 2010 年至 2025 年间发表的研究进行了结构化文献检索。符合条件的出版物包括涉及基于抗体的疗法、肿瘤微环境屏障和计算创新的临床前研究、临床试验和综述。数据被综合为以下主题类别:耐药机制、基于抗体的平台、纳米技术辅助递送和人工智能(AI)驱动的策略。抗体治疗药物,包括单克隆抗体、抗体-药物偶联物、双特异性抗体和光免疫疗法,显示出增强肿瘤靶向和免疫激活的潜力。血脑屏障、免疫抑制性细胞浸润和肿瘤异质性等关键障碍显著限制了疗效。新型方法,包括 AI 赋能的抗体设计、数字孪生建模和生物标志物驱动的患者分层,为提高精准性和克服耐药提供了机会。与放疗、疫苗或过继性细胞疗法的联合策略进一步拓展了治疗潜力。通过从屏障解除和技术整合的视角重新审视抗体治疗,本综述将基于抗体的方法定位为未来 GBM 管理的现实支柱。递送、工程和计算建模方面的战略性创新可能将抗体从实验工具转变为这种致死性恶性肿瘤的基石疗法。
Glioblastoma (GBM) remains the most aggressive adult brain tumor, with median survival largely unchanged over two decades. Antibody-based therapies have shown promise in hematologic and systemic cancers, but translation to GBM has been hindered by the tumor's hostile microenvironment and immune evasion mechanisms. A structured literature search was conducted in PubMed, Scopus, Web of Science, and ClinicalTrials. gov for studies published between 2010 and 2025. Eligible publications included preclinical investigations, clinical trials, and reviews addressing antibody-based therapies, tumor microenvironmental barriers, and computational innovations. Data were synthesized into thematic categories: mechanisms of resistance, antibody-based platforms, nanotechnology-assisted delivery, and artificial intelligence (AI)-driven strategies.
Antibody therapeutics including monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, and photoimmunotherapy show potential to enhance tumor targeting and immune activation. Key barriers such as the blood-brain barrier, immunosuppressive cell infiltration, and tumor heterogeneity significantly restrict efficacy. Novel approaches, including AI-enabled antibody design, digital twin modeling, and biomarker-driven patient stratification, offer opportunities to improve precision and overcome resistance.
Combination strategies with radiotherapy, vaccines, or adoptive cell therapies further expand therapeutic potential. By reframing antibody therapy through the lens of barrier disarmament and technological integration, this review positions antibody-based approaches as realistic pillars of future GBM management. Strategic innovations in delivery, engineering, and computational modeling may transform antibodies from experimental tools into cornerstone therapies for this lethal malignancy.
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