title: Moving oncolytic viruses into the clinic: clinical-grade production, purification, and characterization of diverse oncolytic viruses.
abstract: Oncolytic viruses (OVs) are unique anticancer agents based on their pleotropic modes of action, which include, besides viral tumor cell lysis, activation of antitumor immunity. A panel of diverse viruses, often genetically engineered, has advanced to clinical investigation, including phase 3 studies. This diversity of virotherapeutics not only offers interesting opportunities for the implementation of different therapeutic regimens but also poses challenges for clinical translation. Thus, manufacturing processes and regulatory approval paths need to be established for each OV individually. This review provides an overview of clinical-grade manufacturing procedures for OVs using six virus families as examples, and key challenges are discussed individually. For example, different virus features with respect to particle size, presence/absence of an envelope, and host species imply specific requirements for measures to ensure sterility, for handling, and for determination of appropriate animal models for toxicity testing, respectively. On the other hand, optimization of serum-free culture conditions, increasing virus yields, development of scalable purification strategies, and formulations guaranteeing long-term stability are challenges common to several if not all OVs. In light of the recent marketing approval of the first OV in the Western world, strategies for further upscaling OV manufacturing and optimizing product characterization will receive increasing attention.
authors.affiliation: Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Department of Translational Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg, Germany; Department of Medical Oncology, National Center for Tumor Diseases and University Hospital, Heidelberg, Germany.
authors.forename: Guy
authors.initials: G
authors.lastname: Ungerechts
authors.affiliation: Centre for Innovative Cancer Research, Ottawa Hospital Research Institute , Ottawa, Ontario, Canada.
authors.forename: Sascha
authors.initials: S
authors.lastname: Bossow
authors.affiliation: Department of Tumor Virology, Infection, Inflammation and Cancer program, German Cancer Research Center (DKFZ) , Heidelberg, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Leuchs
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technical University Munich , Munich, Germany.
authors.forename: Per S
authors.initials: PS
authors.lastname: Holm
authors.affiliation: Department of Tumor Virology, Infection, Inflammation and Cancer program, German Cancer Research Center (DKFZ) , Heidelberg, Germany.
authors.forename: Jean
authors.initials: J
authors.lastname: Rommelaere
authors.affiliation: Oncolytics Biotech Inc. , Calgary, Alberta, Canada.
authors.forename: Matt
authors.initials: M
authors.lastname: Coffey
authors.affiliation: Replimune Ltd , Oxford, UK.
authors.forename: Rob
authors.initials: R
authors.lastname: Coffin
authors.affiliation: Centre for Innovative Cancer Research, Ottawa Hospital Research Institute , Ottawa, Ontario, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Bell
authors.affiliation: German Cancer Research Center (DKFZ) , Heidelberg, Germany.
authors.forename: Dirk M
authors.initials: DM
authors.lastname: Nettelbeck