Department of Gene Therapy, Ulm University, Ulm, Germany.
Hum Gene Ther. 2020 Oct;31(19-20):1100-1113. doi: 10.1089/hum.2020.045. Epub 2020 Aug 17.
Oncolytic viruses are promising anticancer agents; however, regarding their clinical efficacy, there is still significant scope for improvement. Preclinical evaluation of oncolytic viruses is mainly based on syngeneic or xenograft tumor models in mice, which is labor-intensive and time-consuming. Currently, a large proportion of developmental work in the research field of oncolytic viruses is directed toward overcoming cellular and noncellular barriers to achieve improved virus delivery to primary tumors and metastases. To evaluate the large number of genetically or chemically modified viruses regarding tumor delivery and biodistribution patterns, it would be valuable to have an model available that would allow easy screening experiments, that is of higher complexity than monoclonal cell lines, and that could be used as a platform method before confirmatory studies in small and large animals. Based on our data, we believe that the chicken chorioallantoic membrane (CAM) assay is a quick and low-cost high-throughput tumor model system for the analysis of oncolytic viruses. Here we describe the establishment, careful characterization, and optimization of the CAM model as an model for the evaluation of oncolytic viruses. We have used human adenovirus type 5 (HAdV-5) as an example for validation but are confident that the model can be used as a test system for replicating viruses of many different virus families. We show that the CAM tumor model enables intratumoral and intravenous virus administration and is a feasible and conclusive model for the analysis of relevant virus-host interactions, biodistribution patterns, and tumor-targeting profiles.
溶瘤病毒是很有前途的抗癌药物；然而，就其临床疗效而言，仍有很大的改进空间。溶瘤病毒的临床前评估主要基于小鼠的同基因或异种移植肿瘤模型，这是一项劳动密集型且耗时的工作。目前，溶瘤病毒研究领域的大部分开发工作都致力于克服细胞和非细胞屏障，以实现对原发性肿瘤和转移瘤的改良病毒递送来提高疗效。为了评估大量经过基因或化学修饰的病毒在肿瘤递送上的差异和生物分布模式，如果有一种模型可以提供便利的筛选实验，其复杂性高于单克隆细胞系，并且可以在小动物和大动物的确认性研究之前作为平台方法使用，那么这将是非常有价值的。基于我们的数据，我们相信鸡胚尿囊膜（CAM）检测是一种快速、低成本、高通量的肿瘤模型系统，可用于分析溶瘤病毒。在此，我们描述了 CAM 模型的建立、仔细的特征描述和优化，将其作为评价溶瘤病毒的模型。我们以人腺病毒 5 型（HAdV-5）为例进行了验证，但有信心该模型可作为用于复制许多不同病毒科的复制病毒的测试系统。我们表明，CAM 肿瘤模型可进行肿瘤内和静脉内病毒给药，是分析相关病毒-宿主相互作用、生物分布模式和肿瘤靶向特征的可行且结论性的模型。
