Robinson Steven, Galanis Evanthia
a Division of Medical Oncology , Mayo Clinic , Rochester , MN , USA.
Expert Opin Biol Ther. 2017 Mar;17(3):353-363. doi: 10.1080/14712598.2017.1288713.
Oncolytic viruses represent a novel treatment modality that is unencumbered by the standard resistance mechanisms limiting the therapeutic efficacy of conventional antineoplastic agents. Attenuated engineered measles virus strains derived from the Edmonston vaccine lineage have undergone extensive preclinical evaluation with significant antitumor activity observed in a broad range of preclinical tumoral models. These have laid the foundation for several clinical trials in both solid and hematologic malignancies, which have demonstrated safety, biologic activity and the ability to elicit antitumor immune responses. Areas covered: This review examines the published preclinical data which supported the clinical translation of this therapeutic platform, reviews the available clinical trial data and expands on ongoing phase II testing. It also looks at approaches to optimize clinical applicability and offers future perspectives. Expert opinion: Reverse genetic engineering has allowed the generation of oncolytic MV strains retargeted to increase viral tumor specificity, or armed with therapeutic and immunomodulatory genes in order to enhance anti-tumor efficacy. Continuous efforts focusing on exploring methods to overcome resistance pathways and determining optimal combinatorial strategies will facilitate further development of this encouraging antitumor strategy.
溶瘤病毒代表了一种新型治疗方式,不受限制传统抗肿瘤药物治疗效果的标准耐药机制的影响。源自埃德蒙斯顿疫苗株系的减毒工程麻疹病毒株已进行了广泛的临床前评估,在广泛的临床前肿瘤模型中观察到显著的抗肿瘤活性。这些为实体瘤和血液系统恶性肿瘤的多项临床试验奠定了基础,这些试验已证明了安全性、生物学活性以及引发抗肿瘤免疫反应的能力。涵盖领域:本综述审视了支持该治疗平台临床转化的已发表临床前数据,回顾了可用的临床试验数据,并详述了正在进行的II期试验。它还探讨了优化临床适用性的方法并提供了未来展望。专家观点:反向基因工程已使得能够产生重新靶向以提高病毒肿瘤特异性的溶瘤麻疹病毒株,或携带治疗性和免疫调节基因以增强抗肿瘤疗效。持续致力于探索克服耐药途径的方法并确定最佳联合策略将促进这一令人鼓舞的抗肿瘤策略的进一步发展。