Preclinical evaluation of engineered oncolytic herpes simplex virus for the treatment of pediatric solid tumors.
Recently, investigators showed that mice with syngeneic murine gliomas that were treated with a neuroattenuated oncolytic herpes simplex virus-1 (oHSV), M002, had a significant increase in survival. M002 has deletions in both copies of the γ134.5 gene, enabling replication in tumor cells but precluding infection of normal cells. Previous studies have shown antitumor effects of other oHSV against a number of adult tumors including hepatocellular carcinoma and renal cell carcinoma. The purpose of the current study was to investigate the oncolytic potential of M002 against difficult to treat pediatric liver and kidney tumors. We showed that the oHSV, M002, infected, replicated, and decreased cell survival in hepatoblastoma, malignant rhabdoid kidney tumor, and renal sarcoma cell lines. In addition, we showed that in murine xenografts, treatment with M002 significantly increased survival and decreased tumor growth. Finally, these studies showed that the primary entry protein for oHSV, CD111 (nectin-1) was present in human hepatoblastoma and malignant rhabdoid kidney tumor specimens. We concluded that M002 effectively targeted these rare aggressive tumor types and that M002 may have potential for use in children with unresponsive or relapsed pediatric solid tumors.
Department of Surgery, Division of Pediatric Surgery, University of Alabama, Birmingham, Birmingham, Alabama, United States of America.
Michael L
ML
Megison
Department of Surgery, Division of Pediatric Surgery, University of Alabama, Birmingham, Birmingham, Alabama, United States of America.
Lauren A
LA
Gillory
Department of Surgery, Division of Pediatric Surgery, University of Alabama, Birmingham, Birmingham, Alabama, United States of America.
Jerry E
JE
Stewart
Department of Surgery, Division of Pediatric Surgery, University of Alabama, Birmingham, Birmingham, Alabama, United States of America.
Hugh C
HC
Nabers
Department of Pathology, Children's of Alabama, Birmingham, Alabama, United States of America.
Elizabeth
E
Mroczek-Musulman
Department of Surgery, Division of Pediatric Surgery, University of Alabama, Birmingham, Birmingham, Alabama, United States of America.
Alicia M
AM
Waters
Department of Surgery, Division of Neurosurgery, University of Alabama, Birmingham, Birmingham, Alabama, United States of America.
Jennifer M
JM
Coleman
Department of Pediatrics, Division of Hematology/Oncology, University of Alabama, Birmingham, Birmingham, Alabama, United States of America.
Virginia
V
Kelly
Department of Surgery, Division of Neurosurgery, University of Alabama, Birmingham, Birmingham, Alabama, United States of America.
James M
JM
Markert
Department of Surgery, Division of Neurosurgery, University of Alabama, Birmingham, Birmingham, Alabama, United States of America.
G Yancey
GY
Gillespie
Department of Pediatrics, Division of Hematology/Oncology, University of Alabama, Birmingham, Birmingham, Alabama, United States of America.
Gregory K
GK
Friedman
Department of Surgery, Division of Pediatric Surgery, University of Alabama, Birmingham, Birmingham, Alabama, United States of America.
Elizabeth A
EA
Beierle
D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000473:pathology / Q000628:therapy*; D008113:Liver Neoplasms / Q000473:pathology / Q000628:therapy*; D008819:Mice, Nude; D000075983:Nectins; D009368:Neoplasm Transplantation; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics*; D018335:Rhabdoid Tumor / Q000473:pathology / Q000628:therapy*; D012512:Sarcoma, Ewing / Q000473:pathology / Q000628:therapy*; D018139:Simplexvirus / Q000235:genetics*; D047368:Tumor Burden; D014779:Virus Replication
D015815:Cell Adhesion Molecules; C000619010:NECTIN1 protein, human; C000619015:Nectin1 protein, mouse; D000075983:Nectins