Title:Oncolytic Herpes Simplex Virus Vectors Fully Retargeted to Tumor- Associated Antigens
Volume: 18
Issue: 2
Author(s): Hiroaki Uchida*, Hirofumi Hamada, Kenji Nakano, Heechung Kwon, Hideaki Tahara, Justus B. Cohen and Joseph C. Glorioso
Affiliation:
- Division of Bioengineering, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo,Japan
Keywords:
Cancer, gene therapy, herpes simplex virus, oncolytic virus, targeting, vector, virotherapy, virus entry.
Abstract: 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.
