肿瘤细胞治疗研究
英文原题：Glioblastoma Immunotherapy: A Systematic Review of the Present Strategies and Prospects for Advancements.
该系统综述中的所有研究均为临床试验，时间跨度为 1995 年至 2023 年，共纳入 6383 例患者。
胶质母细胞瘤（GBM）具有侵袭性强、复发率高的特点。尽管常规治疗有所进步，GBM患者预后仍然较差。免疫疗法近来成为一种潜在治疗选择。本系统综述旨在评估GBM免疫治疗的现行策略及未来发展方向。截至2023年9月3日，研究人员系统检索了PubMed、Embase和Cochrane Library等主要医学数据库，采用与“胶质母细胞瘤”“免疫疗法”和“治疗”相关的医学主题词及关键词。纳入研究包括报告免疫疗法用于人类胶质瘤治疗的随机对照试验、非随机对照试验及队列研究。初步检索共发现1588篇论文，其中752篇符合资格；655篇因多种原因被排除，包括与主题无关（627篇）、方法或结果信息不足（12篇）、病例系列或队列研究（22篇）、系统综述或荟萃分析（3篇）。综述纳入的研究均为1995至2023年开展的临床试验，共涉及6383例患者。Neuro-Oncology发表的胶质瘤免疫治疗相关临床试验最多，为15/97（16%）。多数研究发表于2018至2022年，这一时期平均每年发表9篇。过继细胞转移类嵌合抗原受体（CAR）T细胞是11%研究的主要关注点；免疫检查点抑制剂（ICI）、溶瘤病毒（OV）和癌症疫苗（CV）分别占26%、12%和51%。I期试验占多数（51%），III期仅占7%；其中60%为单臂试验，39%为双臂试验，另有1项多臂试验。免疫疗法主要用于复发性GBM（55%）。综述还发现正在开展的临床试验包括9项ICI、7项CV、10项OV及8项CAR-T试验，共34项；其中I期占多数（53%），仅1项为III期。克服免疫耐受、诱导强效肿瘤抗原应答并对抗免疫抑制性微环境，是实现GBM治愈性免疫治疗的关键。PD-1和CTLA-4抑制剂等免疫检查点抑制剂显示出潜力，当前研究正致力于增强其疗效。个体化癌症疫苗，尤其是靶向新抗原的疫苗，具有显著潜力。溶瘤病毒具有双重作用机制，并在临床试验中取得突破。针对特定抗原构建的CAR-T疗法已显示出令人鼓舞的结果，尤其是靶向IL13Rα2和EGFRvIII的疗法。具有更高特异性的第二代CAR-T细胞的开发，体现了这一策略的可塑性。
Glioblastoma (GBM) is characterized by aggressive growth and high rates of recurrence. Despite the advancements in conventional therapies, the prognosis for GBM patients remains poor. Immunotherapy has recently emerged as a potential treatment option. The aim of this systematic review is to assess the current strategies and future perspectives of the GBM immunotherapy strategies. A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to 3 September 2023. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to "glioblastomas," "immunotherapies," and "treatment." The studies included in this review consist of randomized controlled trials, non-randomized controlled trials, and cohort studies reporting on the use of immunotherapies for the treatment of gliomas in human subjects. A total of 1588 papers are initially identified. Eligibility is confirmed for 752 articles, while 655 are excluded for various reasons, including irrelevance to the research topic (627), insufficient method and results details (12), and being case-series or cohort studies (22), systematic literature reviews, or meta-analyses (3). All the studies within the systematic review were clinical trials spanning from 1995 to 2023, involving 6383 patients. Neuro-oncology published the most glioma immunotherapy-related clinical trials (15/97, 16%). Most studies were released between 2018 and 2022, averaging nine publications annually during this period. Adoptive cellular transfer chimeric antigen receptor (CAR) T cells were the primary focus in 11% of the studies, with immune checkpoint inhibitors (ICIs), oncolytic viruses (OVs), and cancer vaccines (CVs) comprising 26%, 12%, and 51%, respectively. Phase-I trials constituted the majority at 51%, while phase-III trials were only 7% of the total. Among these trials, 60% were single arm, 39% double arm, and one multi-arm. Immunotherapies were predominantly employed for recurrent GBM (55%). The review also revealed ongoing clinical trials, including 9 on ICIs, 7 on CVs, 10 on OVs, and 8 on CAR T cells, totaling 34 trials, with phase-I trials representing the majority at 53%, and only one in phase III. Overcoming immunotolerance, stimulating robust tumor antigen responses, and countering immunosuppressive microenvironment mechanisms are critical for curative GBM immunotherapy. Immune checkpoint inhibitors, such as PD-1 and CTLA-4 inhibitors, show promise, with the ongoing research aiming to enhance their effectiveness. Personalized cancer vaccines, especially targeting neoantigens, offer substantial potential. Oncolytic viruses exhibited dual mechanisms and a breakthrough status in the clinical trials. CAR T-cell therapy, engineered for specific antigen targeting, yields encouraging results, particularly against IL13 R 2 and EGFRvIII. The development of second-generation CAR T cells with improved specificity exemplifies their adaptability.
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