肿瘤细胞治疗研究
英文原题：Role of Adenoviruses in Cancer Therapy.
癌症是全球主要死亡原因之一，仅次于心脏病，位居第二。
癌症是世界上主要的死亡原因之一，仅次于心脏病，位居第二。腺病毒（Ads）已成为癌症治疗新治疗策略的希望。本综述的目的是讨论腺病毒载体在癌症治疗中应用的最新进展。腺病毒载体可以通过不同方式进行工程化改造，从而将肿瘤微环境从冷肿瘤转变为热肿瘤，包括：1. 通过改造 Ads 以递送编码肿瘤抑制基因（p53）和其他其表达导致细胞周期阻滞的蛋白质的转基因；2. Ads 也可以被改造以表达肿瘤特异性抗原、细胞因子和其他免疫调节分子。在癌症治疗中使用 Ads 的另一种策略是使用溶瘤腺病毒，其直接杀死肿瘤细胞。Gendicine 和 Advexin 是复制缺陷型重组人 p53 腺病毒载体，已被证明对多种类型的癌症有效。Gendicine 于 2003 年被中国食品药品监督管理局（FDA）机构批准用于治疗头颈部鳞状细胞癌，作为首个基因治疗产品。Oncorine 和 ONYX-015 是溶瘤腺病毒载体，已被证明对某些类型的癌症有效。中国 FDA 机构也已批准 Oncorin 用于治疗头颈部癌症。被工程化改造以表达免疫刺激性细胞因子和其他免疫调节分子如 TNF-α、IL-2、BiTE、CD40L、4-1BBL、GM-CSF 和 IFN 的 Ads 在癌症治疗中已显示出有希望的结果。Ads 还可以提高免疫检查点抑制剂和过继性细胞疗法（CAR-T 细胞）的治疗疗效。此外，作为抗癌疫苗测试的不同复制缺陷型腺病毒载体（Ad5-CEA、Ad5-PSA、Ad-E6E7、ChAdOx1-MVA和Ad转导的树突状细胞）已被证明可诱导强烈的抗肿瘤免疫反应。然而，腺病毒载体在基因治疗中的应用受到若干因素的限制，例如对腺病毒载体的预存免疫以及病毒的高免疫原性。因此，必须不断开发创新策略，以克服在基因治疗中使用腺病毒载体的障碍。
Cancer is one of the leading causes of death in the world, which is the second after heart diseases. Adenoviruses (Ads) have become the promise of new therapeutic strategy for cancer treatment. The objective of this review is to discuss current advances in the applications of adenoviral vectors in cancer therapy. Adenoviral vectors can be engineered in different ways so as to change the tumor microenvironment from cold tumor to hot tumor, including; 1. by modifying Ads to deliver transgenes that codes for tumor suppressor gene (p53) and other proteins whose expression result in cell cycle arrest 2. Ads can also be modified to express tumor specific antigens, cytokines, and other immune-modulatory molecules. The other strategy to use Ads in cancer therapy is to use oncolytic adenoviruses, which directly kills tumor cells. Gendicine and Advexin are replication-defective recombinant human p53 adenoviral vectors that have been shown to be effective against several types of cancer. Gendicine was approved for treatment of squamous cell carcinoma of the head and neck by the Chinese Food and Drug Administration (FDA) agency in 2003 as a first-ever gene therapy product. Oncorine and ONYX-015 are oncolytic adenoviral vectors that have been shown to be effective against some types of cancer. The Chiness FDA agency has also approved Oncorin for the treatment of head and neck cancer. Ads that were engineered to express immune-stimulatory cytokines and other immune-modulatory molecules such as TNF-α, IL-2, BiTE, CD40L, 4-1BBL, GM-CSF, and IFN have shown promising outcome in treatment of cancer. Ads can also improve therapeutic efficacy of immune checkpoint inhibitors and adoptive cell therapy (Chimeric Antigen Receptor T Cells). In addition, different replication-deficient adenoviral vectors (Ad5-CEA, Ad5-PSA, Ad-E6E7, ChAdOx1-MVA and Ad-transduced Dendritic cells) that were tested as anticancer vaccines have been demonstrated to induce strong antitumor immune response. However, the use of adenoviral vectors in gene therapy is limited by several factors such as pre-existing immunity to adenoviral vectors and high immunogenicity of the viruses. Thus, innovative strategies must be continually developed so as to overcome the obstacles of using adenoviral vectors in gene therapy.
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