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:Recurrent Glioblastoma and the Tumor Immune Landscape: Emerging Immunotherapeutic Strategies.
Recurrent Glioblastoma and the Tumor Immune Landscape: Emerging Immunotherapeutic Strategies.
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胶质母细胞瘤(GBM)是累及中枢神经系统最具侵袭性的恶性肿瘤。当前的标准治疗仅能提供有限的临床获益,多数患者最终出现肿瘤复发,此时治疗选择明显受限,预后仍然极差。近年来,免疫治疗在多种实体瘤中取得了显著的临床成功,凭借其特异性和强效抗肿瘤活性,已成为晚期癌症的关键治疗策略。
然而,复发胶质母细胞瘤(rGBM)的免疫抑制性肿瘤微环境、其显著的异质性以及血脑屏障的存在,共同削弱了免疫治疗的疗效。随着对肿瘤微环境和免疫逃逸机制认识的不断深入,以及免疫治疗策略的不断完善,免疫治疗最终可能成为rGBM患者的治疗选择之一。目前,正在研究中的rGBM主要免疫治疗包括免疫检查点抑制剂、CAR-T 细胞疗法、溶瘤病毒疗法和癌症疫苗。在本综述中,我们全面总结了这些方法的临床证据,重点阐述其作用机制,并批判性评估限制临床转化的关键挑战。通过整合近期治疗进展与尚未解决的障碍,我们旨在为rGBM免疫治疗的优化提供及时的视角,并为未来临床试验的合理设计提供参考。
Glioblastoma (GBM) is the most aggressive malignant tumor affecting the central nervous system. Current standard of care provides only modest clinical benefits, most patients eventually develop tumor recurrence, at which point therapeutic options become markedly restricted and the prognosis remains dismal. In recent years, immunotherapy has achieved significant clinical success in several solid tumors and has become a key strategy for advanced cancers owing to its specificity and potent antitumor activity. Nevertheless, the immunosuppressive tumor microenvironment of recurrent GBM (rGBM), along with its pronounced heterogeneity, and the presence of blood-brain barrier collectively undermine the efficacy of immunotherapy.
With increasing insights into the tumor microenvironment and immune escape mechanisms, alongside refinements in immunotherapeutic strategies, immunotherapy may ultimately become one of the therapeutic options for patients with rGBM. Currently, principal immunotherapies under investigation for rGBM include immune checkpoint inhibitors, CAR-T cell therapy, oncolytic virotherapy, and cancer vaccines.
In this review, we comprehensively summarize the clinical evidence for these approaches, highlight their mechanisms of action, and critically evaluate the key challenges that limit clinical translation. By integrating recent therapeutic progress and unresolved obstacles, we aim to provide a timely perspective on the optimization of immunotherapy in rGBM and to inform the rational design of future clinical trials.
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