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Oncolytic Herpes Simplex Virus Vectors Fully Retargeted to Tumor- Associated Antigens

[ Vol. 18 , Issue. 2 ]

Author(s):

Hiroaki Uchida*, Hirofumi Hamada, Kenji Nakano, Heechung Kwon, Hideaki Tahara, Justus B. Cohen and Joseph C. GloriosoPages 162-170 (9)

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.

Keywords:

Cancer, gene therapy, herpes simplex virus, oncolytic virus, targeting, vector, virotherapy, virus entry.

Affiliation:

Division of Bioengineering, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Department of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Tokyo, Innovation Center for Medical Redox Navigation, Kyushu University, Fukuoka, Division of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul, Division of Bioengineering, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pennsylvania, PA, Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pennsylvania, PA

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