McKenna Mary K, Rosewell-Shaw Amanda, Suzuki Masataka
Baylor College of Medicine, Center for Cell Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Houston, TX 77030, USA.
Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Cancers (Basel). 2020 Mar 7;12(3):619. doi: 10.3390/cancers12030619.
Oncolytic adenoviruses (OAd) selectively target and lyse tumor cells and enhance anti- tumor immune responses. OAds have been used as promising cancer gene therapies for many years and there are a multitude of encouraging pre-clinical studies. However, translating OAd therapies to the clinic has had limited success, in part due to the lack of realistic pre-clinical models to rigorously test the efficacy of OAds. Solid tumors have a heterogenous and hostile microenvironment that provides many barriers to OAd treatment, including structural and immunosuppressive components that cannot be modeled in two-dimensional tissue culture. To replicate these characteristics and bridge the gap between pre-clinical and clinical success, studies must test OAd therapy in three-dimensional culture and animal models. This review focuses on current methods to test OAd efficacy in vitro and in vivo and the development of new model systems to test both oncolysis and immune stimulatory components of oncolytic adenovirotherapy.
溶瘤腺病毒（OAd）可选择性地靶向并裂解肿瘤细胞，增强抗肿瘤免疫反应。多年来，溶瘤腺病毒一直被用作有前景的癌症基因疗法，并且有大量令人鼓舞的临床前研究。然而，将溶瘤腺病毒疗法转化到临床的成效有限，部分原因是缺乏逼真的临床前模型来严格测试溶瘤腺病毒的疗效。实体瘤具有异质性且恶劣的微环境，这为溶瘤腺病毒治疗带来了诸多障碍，包括无法在二维组织培养中模拟的结构和免疫抑制成分。为了复制这些特征并弥合临床前和临床成功之间的差距，研究必须在三维培养和动物模型中测试溶瘤腺病毒疗法。本综述聚焦于当前在体外和体内测试溶瘤腺病毒疗效的方法，以及用于测试溶瘤腺病毒疗法的溶瘤作用和免疫刺激成分的新模型系统的开发。
