| 曾雨欣,刘玉琴,祁 瑞,等.腺病毒载体在恶性肿瘤治疗中预存免疫挑战及应对策略[J].肿瘤学杂志,2025,31(11):996-1002. |
| 腺病毒载体在恶性肿瘤治疗中预存免疫挑战及应对策略 |
| The Challenges and Countermeasures on Pre-existing Immunity of Adenovirus Vectors in the Treatment of Malignant Tumors |
| 投稿时间：2024-11-16 |
| DOI：10.11735/j.issn.1671-170X.2025.11.B010 |
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| 中文关键词: 腺病毒载体 恶性肿瘤 预存免疫 免疫逃逸 联合疗法 |
| 英文关键词:adenovirus vector malignant tumor pre-existing immunity immune escape combination therapy |
| 基金项目:甘肃省自然科学基金（23JRRA1800）；兰州市科技计划项目（2018-1-122） |
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| 中文摘要: |
| 摘 要：腺病毒载体因其高效转染能力、大容量基因装载和卓越的肿瘤靶向性，已成为肿瘤基因治疗与免疫治疗的重要工具。然而，人群中普遍存在的腺病毒预存免疫可显著削弱载体递送效率，限制临床疗效。全文系统综述了克服这一瓶颈的创新策略：①载体工程化改造：通过修饰衣壳蛋白；②血清型转换：开发稀有血清型嵌合载体，降低中和抗体识别；③化学封装：使用聚乙二醇与介孔二氧化硅纳米颗粒物理隔绝抗体；④外泌体递送系统：通过生物膜伪装、物理屏障逃避及免疫调节抗体实现高效靶向递送；⑤免疫调节干预：联合免疫抑制剂、载体预给药诱导免疫耐受或利用佐剂重塑免疫微环境。临床前及早期临床试验表明，上述策略可有效降低预存免疫影响，增强抗肿瘤免疫应答。未来研究需深入探索个体化免疫逃避方案，并推动联合疗法在晚期实体瘤中的转化应用。 |
| 英文摘要: |
| Abstract： Adenovirus vectors have emerged as important tools for tumor gene therapy and immunotherapy due to their efficient transfection ability， large capacity for gene loading， and excellent tumor targeting properties. However， the widespread pre-existing immunity to adenoviruses can significantly reduce the delivery efficiency of the vectors and limit clinical efficacy. This paper systematically reviews innovative strategies to overcome this bottleneck： ①vector engineering： by modifying the capsid proteins； ②serotype conversion： developing rare serotype chimeric vectors to reduce neutralizing antibody recognition； ③chemical encapsulation： using polyethylene glycol and mesoporous silica nanoparticle to physically separate antibodies； ④exosome delivery system： achieving efficient targeted delivery through biological membrane camouflage， physical barrier avoidance， and immune-regulating antibodies； ⑤immune modulation intervention： combining immunosuppressants， pre-administration of vectors to induce immune tolerance， or using adjuvants to reshape the immune microenvironment. Preclinical and early clinical trials have shown that these strategies can effectively reduce the impact of pre-existing immunity and enhance anti-tumor immune responses. Future research needs to deeply explore individualized immune evasion strategies and promote the translational application of combined therapies in advanced solid tumors. |
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