title: Pediatric cancer gone viral. Part I: strategies for utilizing oncolytic herpes simplex virus-1 in children.
abstract: Progress for improving outcomes in pediatric patients with solid tumors remains slow. In addition, currently available therapies are fraught with numerous side effects, often causing significant life-long morbidity for long-term survivors. The use of viruses to kill tumor cells based on their increased vulnerability to infection is gaining traction, with several viruses moving through early and advanced phase clinical testing. The prospect of increased efficacy and decreased toxicity with these agents is thus attractive for pediatric cancer. In part I of this two-part review, we focus on strategies for utilizing oncolytic engineered herpes simplex virus (HSV) to target pediatric malignancies. We discuss mechanisms of action, routes of delivery, and the role of preexisting immunity on antitumor efficacy. Challenges to maximizing oncolytic HSV in children are examined, and we highlight how these may be overcome through various arming strategies. We review the preclinical and clinical evidence demonstrating safety of a variety of oncolytic HSVs. In Part II, we focus on the antitumor efficacy of oncolytic HSV in pediatric tumor types, pediatric clinical advances made to date, and future prospects for utilizing HSV in pediatric patients with solid tumors.
authors.affiliation: Division of Hematology/Oncology/Blood and Marrow Transplantation, Cancer and Blood Diseases, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio, USA ; Center for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Cripe
authors.affiliation: Division of Hematology/Oncology/Blood and Marrow Transplantation, Cancer and Blood Diseases, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio, USA ; Center for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Center for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Denton
authors.affiliation: Division of Hematology/Oncology/Blood and Marrow Transplantation, Cancer and Blood Diseases, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio, USA ; Center for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Kellie B
authors.initials: KB
authors.lastname: Haworth
authors.affiliation: Center for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Hutzen
authors.affiliation: Center for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Leddon
authors.affiliation: Division of Hematology/Oncology/Blood and Marrow Transplantation, Cancer and Blood Diseases, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio, USA ; Center for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Keri A
authors.initials: KA
authors.lastname: Streby
authors.affiliation: Center for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Pin-Yi
authors.initials: PY
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Markert
authors.affiliation: Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Alicia M
authors.initials: AM
authors.lastname: Waters
authors.affiliation: Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: George Yancey
authors.initials: GY
authors.lastname: Gillespie
authors.affiliation: Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Beierle
authors.affiliation: Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Gregory K
authors.initials: GK
authors.lastname: Friedman