Oncolytic herpes simplex virus tumor targeting and neutralization escape by engineering viral envelope glycoproteins

Xiao-Qin Liu; Hong-Yi Xin; Yan-Ning Lyu; Zhao-Wu Ma; Xiao-Chun Peng; Ying Xiang; Ying-Ying Wang; Zi-Jun Wu; Jun-Ting Cheng; Jia-Fu Ji; Ji-Xin Zhong; Bo-Xu Ren; Xian-Wang Wang; Hong-Wu Xin

doi:10.1080/10717544.2018.1534895

Oncolytic herpes simplex virus tumor targeting and neutralization escape by engineering viral envelope glycoproteins

Drug Deliv. 2018 Nov;25(1):1950-1962. doi: 10.1080/10717544.2018.1534895.

Authors

Xiao-Qin Liu^{1

2

3

4}, Hong-Yi Xin⁵, Yan-Ning Lyu⁶, Zhao-Wu Ma^{1

2

3}, Xiao-Chun Peng^{1

2

7}, Ying Xiang^{1

2

3}, Ying-Ying Wang^{1

2

3}, Zi-Jun Wu^{1

2

3

4}, Jun-Ting Cheng^{1

2

3}, Jia-Fu Ji⁸, Ji-Xin Zhong⁹, Bo-Xu Ren^{1

4}, Xian-Wang Wang^{1

2

10}, Hong-Wu Xin^{1

2

3}

Affiliations

¹ a Faculty of Medicine, The Second School of Clinical Medicine , Yangtze University, Nanhuan , Jingzhou , Hubei , China.
² b Laboratory of Oncology, Faculty of Medicine, Center for Molecular Medicine, School of Basic Medicine , Yangtze University , Jingzhou , Hubei , China.
³ c Faculty of Medicine, Department of Biochemistry and Molecular Biology, School of Basic Medicine , Yangtze University , Jingzhou , Hubei , China.
⁴ d Department of Nursing and Medical Imaging Technology , Yangtze University , Jingzhou , Hubei , China.
⁵ e Star Array Pte Ltd , JTC Medtech Hub , Singapore , Singapore.
⁶ f Institute for Infectious Diseases and Endemic Diseases Prevention and Control, Beijing Center for Diseases Prevention and Control , Beijing , China.
⁷ g Faculty of Medicine, Department of Pathophysiology, School of Basic Medicine , Yangtze University , Jingzhou , Hubei , China.
⁸ h Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery , Peking University Cancer Hospital and Institute , Haidian , Beijing , China.
⁹ i Cardiovascular Research Institute , Case Western Reserve University , Cleveland , OH , USA.
¹⁰ j Faculty of Medicine, Department of Laboratory Medicine, School of Basic Medicine , Yangtze University , Jingzhou , Hubei , China.

Abstract

Oncolytic herpes simplex viruses (oHSVs) have been approved for clinical usage and become more and more popular for tumor virotherapy. However, there are still many issues for the oHSVs used in clinics and clinical trials. The main issues are the limited anti-tumor effects, intratumor injection, and some side effects. To overcome such challenges, here we review the genetic engineering of the envelope glycoproteins for oHSVs to target tumors specifically, and at the same time we summarize the many neutralization antibodies against the envelope glycoproteins and align the neutralization epitopes with functional domains of the respective glycoproteins for future identification of new functions of the glycoproteins and future engineering of the epitopes to escape from host neutralization.

Keywords: Oncolytic virotherapy; envelope glycoprotein; herpes simplex virus; immune escape; neutralization antibody; tumor targeting.

Publication types

Review

MeSH terms

Antibodies, Neutralizing / immunology
Antibodies, Viral / immunology
Epitopes / genetics
Glycoproteins / genetics*
Humans
Immune Evasion / immunology
Neoplasms / therapy*
Oncolytic Virotherapy / methods*
Protein Engineering / methods*
Simplexvirus / genetics*
Simplexvirus / immunology
Viral Envelope Proteins / genetics*

Substances

Antibodies, Neutralizing
Antibodies, Viral
Epitopes
Glycoproteins
Viral Envelope Proteins
glycoprotein B, Simplexvirus
glycoprotein H, herpes simplex virus type 1
glycoprotein gC, herpes simplex virus type 1
glycoprotein gD, herpes simplex virus type 1

Grants and funding

This work was partly supported by grants from the National Natural Science Foundation of China [81772223 and 81670431 to BXR, 81602303 to YX, 31700736 to XWW, 81872412 to HWX]. We thank Hubei Province Natural Science Foundation of China [2016CFB180 to XWW], Hubei Province Health and Family Planning Scientific Research Project [WJ2016Y07 to XWW], Hubei Province Scientific and Technological Research Project [Q20171306 to XWW], Jingzhou Science and Technology Development Planning Project [JZKJ15063 to XWW], and Yangtze University Fellowship to graduate student (XQL).