title: Pediatric cancer gone viral. Part II: potential clinical application of oncolytic herpes simplex virus-1 in children.
abstract: Oncolytic engineered herpes simplex viruses (HSVs) possess many biologic and functional attributes that support their use in clinical trials in children with solid tumors. Tumor cells, in an effort to escape regulatory mechanisms that would impair their growth and progression, have removed many mechanisms that would have protected them from virus infection and eventual virus-mediated destruction. Viruses engineered to exploit this weakness, like mutant HSV, can be safely employed as tumor cell killers, since normal cells retain these antiviral strategies. Many preclinical studies and early phase trials in adults demonstrated that oncolytic HSV can be safely used and are highly effective in killing tumor cells that comprise pediatric malignancies, without generating the toxic side effects of nondiscriminatory chemotherapy or radiation therapy. A variety of engineered viruses have been developed and tested in numerous preclinical models of pediatric cancers and initial trials in patients are underway. In Part II of this review series, we examine the preclinical evidence to support the further advancement of oncolytic HSV in the pediatric population. We discuss clinical advances made to date in this emerging era of oncolytic virotherapy.
authors.affiliation: Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Gregory K
authors.initials: GK
authors.lastname: Friedman
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 Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: George Yancey
authors.initials: GY
authors.lastname: Gillespie
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: 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: Division of Hematology/Oncology/Blood and Marrow Transplantation, 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: Division of Hematology/Oncology/Blood and Marrow Transplantation, 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: Division of Hematology/Oncology/Blood and Marrow Transplantation, 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: Division of Hematology/Oncology/Blood and Marrow Transplantation, 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: 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