Oncolytic viruses constitute an emerging strategy in immunomodulatory cancer treatment. The first oncolytic virus, Talimogene laherparepvec (T-VEC), based on herpes simplex virus 1 (HSV-1), was approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) in 2015. The field of oncolytic virotherapy is still in its beginnings, since many promising viruses remain only superficially explored. Influenza A virus causes a highly immunogenic acute infection but never leads to a chronic disease. While oncolytic influenza A viruses are in preclinical development, they have not made the transition into clinical practice yet. Recent insights into different types of cell death caused by influenza A virus infection illuminate novel possibilities of enhancing its therapeutic effect. Genetic engineering and experience in influenza A virus vaccine development allow safe application of the virus in patients. In this review we give a summary of efforts undertaken to develop oncolytic influenza A viruses. We discuss strategies for targeting viral replication to cancerous lesions and arming them with immunogenic transgenes. We furthermore describe which modes of cell death are induced by influenza A virus infection and how these insights may be utilized to optimize influenza A virus-based oncolytic virus design.

溶瘤病毒构成了免疫调节癌症治疗的新兴策略。第一个溶瘤病毒Talimogene laherparepvec（T-VEC）基于单纯疱疹病毒1（HSV-1），于2015年获得美国食品药品监督管理局（FDA）和欧洲药品管理局（EMA）批准。病毒疗法仍处于起步阶段，因为许多有希望的病毒仍只是表面探索。甲型流感病毒会引起高度免疫原性的急性感染，但不会导致慢性疾病。虽然溶瘤甲型流感病毒正处于临床前开发阶段，但尚未过渡到临床实践。最近对甲型流感病毒感染引起的不同类型细胞死亡的见解揭示了增强其治疗效果的新可能性。基因工程和甲型流感病毒疫苗开发经验使该病毒能够安全地应用于患者。在这篇综述中，我们总结了开发甲型溶瘤流感病毒所付出的努力。我们讨论了将病毒复制靶向癌性病变并用免疫原性转基因武装它们的策略。我们还描述了甲型流感病毒感染诱导哪些细胞死亡模式，以及如何利用这些见解来优化基于甲型流感病毒的溶瘤病毒设计。