Oncolytic Herpes Simplex Virus Vectors Fully Retargeted to Tumor- Associated Antigens.
Oncolytic virotherapy is a novel therapeutic modality for malignant diseases that exploits selective viral replication in cancer cells. Herpes simplex virus (HSV) is a promising agent for oncolytic virotherapy due to its broad cell tropism and the identification of mutations that favor its replication in tumor over normal cells. However, these attenuating mutations also tend to limit the potency of current oncolytic HSV vectors that have entered clinical studies. As an alternative, vector retargeting to novel entry receptors has the potential to achieve tumor specificity at the stage of virus entry, eliminating the need for replication-attenuating mutations. Here, we summarize the molecular mechanism of HSV entry and recent advances in the development of fully retargeted HSV vectors for oncolytic virotherapy. Retargeted HSV vectors offer an attractive platform for the creation of a new generation of oncolytic HSV with improved efficacy and specificity.
Division of Bioengineering, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Hiroaki
H
Uchida
Department of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
Hirofumi
H
Hamada
Innovation Center for Medical Redox Navigation, Kyushu University, Fukuoka, Japan.
Kenji
K
Nakano
Division of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
Heechung
H
Kwon
Division of Bioengineering, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Hideaki
H
Tahara
Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pennsylvania, PA, United States.
Justus B
JB
Cohen
Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pennsylvania, PA, United States.
Joseph C
JC
Glorioso
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000276:immunology; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D050130:Oncolytic Virotherapy; D018139:Simplexvirus / Q000235:genetics* / Q000276:immunology
D000951:Antigens, Neoplasm
Cancer; gene therapy; herpes simplex virus; oncolytic virus; targeting; vector; virotherapy; virus entry