Clinical Cooperation Unit Virotherapy, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Department of Medical Oncology, National Center for Tumor Diseases and Heidelberg University Hospital, Im Neuenheimer Feld 460, 69120 Heidelberg, Germany.
Viruses. 2021 Jul 21;13(8):1420. doi: 10.3390/v13081420.
Virotherapy research involves the development, exploration, and application of oncolytic viruses that combine direct killing of cancer cells by viral infection, replication, and spread (oncolysis) with indirect killing by induction of anti-tumor immune responses. Oncolytic viruses can also be engineered to genetically deliver therapeutic proteins for direct or indirect cancer cell killing. In this review-as part of the special edition on "State-of-the-Art Viral Vector Gene Therapy in Germany"-the German community of virotherapists provides an overview of their recent research activities that cover endeavors from screening and engineering viruses as oncolytic cancer therapeutics to their clinical translation in investigator-initiated and sponsored multi-center trials. Preclinical research explores multiple viral platforms, including new isolates, serotypes, or fitness mutants, and pursues unique approaches to engineer them towards increased safety, shielded or targeted delivery, selective or enhanced replication, improved immune activation, delivery of therapeutic proteins or RNA, and redirecting antiviral immunity for cancer cell killing. Moreover, several oncolytic virus-based combination therapies are under investigation. Clinical trials in Germany explore the safety and potency of virotherapeutics based on parvo-, vaccinia, herpes, measles, reo-, adeno-, vesicular stomatitis, and coxsackie viruses, including viruses encoding therapeutic proteins or combinations with immune checkpoint inhibitors. These research advances represent exciting vantage points for future endeavors of the German virotherapy community collectively aimed at the implementation of effective virotherapeutics in clinical oncology.
病毒疗法研究涉及溶瘤病毒的开发、探索和应用，这些病毒将病毒感染、复制和传播（溶瘤作用）直接杀死癌细胞与诱导抗肿瘤免疫反应的间接杀伤作用相结合。溶瘤病毒还可以被设计用于基因传递治疗蛋白，以直接或间接杀死癌细胞。在这篇综述中——作为“德国最新病毒载体基因治疗”特刊的一部分——德国病毒治疗师社区概述了他们最近的研究活动，这些活动涵盖了从筛选和工程溶瘤癌症治疗病毒到在研究者发起的和赞助的多中心试验中进行临床转化的努力。临床前研究探索了多种病毒平台，包括新的分离株、血清型或适应性突变体，并采用独特的方法对其进行工程改造，以提高安全性、屏蔽或靶向递送、选择性或增强复制、改善免疫激活、递送治疗蛋白或 RNA，并重新定向抗病毒免疫以杀死癌细胞。此外，还正在研究几种溶瘤病毒联合治疗方法。德国的临床试验探索了基于细小病毒、牛痘病毒、疱疹病毒、麻疹病毒、副黏病毒、腺病毒、水疱性口炎病毒和柯萨奇病毒的病毒疗法的安全性和效力，包括编码治疗蛋白的病毒或与免疫检查点抑制剂的组合。这些研究进展为德国病毒治疗师社区的未来努力提供了令人兴奋的有利视角，共同旨在将有效的病毒疗法应用于临床肿瘤学。
