Department of Internal Medicine, Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland Medical Center, 22 S. Greene Street, Baltimore, MD 21201, USA.
Department of Internal Medicine-Medical Oncology, University of Kentucky, Lexington, KY 40536, USA.
Int J Mol Sci. 2020 Oct 12;21(20):7505. doi: 10.3390/ijms21207505.
Leveraging the immune system to thwart cancer is not a novel strategy and has been explored via cancer vaccines and use of immunomodulators like interferons. However, it was not until the introduction of immune checkpoint inhibitors that we realized the true potential of immunotherapy in combating cancer. Oncolytic viruses are one such immunotherapeutic tool that is currently being explored in cancer therapeutics. We present the most comprehensive systematic review of all oncolytic viruses in Phase 1, 2, and 3 clinical trials published to date. We performed a systematic review of all published clinical trials indexed in PubMed that utilized oncolytic viruses. Trials were reviewed for type of oncolytic virus used, method of administration, study design, disease type, primary outcome, and relevant adverse effects. A total of 120 trials were found; 86 trials were available for our review. Included were 60 phase I trials, five phase I/II combination trials, 19 phase II trials, and two phase III clinical trials. Oncolytic viruses are feverously being evaluated in oncology with over 30 different types of oncolytic viruses being explored either as a single agent or in combination with other antitumor agents. To date, only one oncolytic virus therapy has received an FDA approval but advances in bioengineering techniques and our understanding of immunomodulation to heighten oncolytic virus replication and improve tumor kill raises optimism for its future drug development.
利用免疫系统来对抗癌症并不是一个新策略，人们已经通过癌症疫苗和使用免疫调节剂（如干扰素）来探索这一策略。然而，直到免疫检查点抑制剂的引入，我们才意识到免疫疗法在抗击癌症方面的真正潜力。溶瘤病毒就是这样一种免疫治疗工具，目前正在癌症治疗中进行探索。我们对迄今为止已发表的所有处于 1 期、2 期和 3 期临床试验阶段的溶瘤病毒进行了最全面的系统综述。我们对 PubMed 中索引的所有已发表的临床研究进行了系统综述，这些研究都使用了溶瘤病毒。对试验中使用的溶瘤病毒类型、给药方法、研究设计、疾病类型、主要结局和相关不良反应进行了评估。共发现 120 项试验，其中 86 项可供我们进行综述。包括 60 项 1 期试验、5 项 1 期/2 期联合试验、19 项 2 期试验和 2 项 3 期临床试验。溶瘤病毒在肿瘤学领域得到了广泛的评估，目前正在探索 30 多种不同类型的溶瘤病毒，它们可以作为单一药物或与其他抗肿瘤药物联合使用。迄今为止，只有一种溶瘤病毒疗法获得了 FDA 的批准，但生物工程技术的进步和我们对免疫调节的理解提高了溶瘤病毒复制和改善肿瘤杀伤的能力，这为其未来的药物开发带来了乐观前景。
