Evaluation of Tumor Specificity and Immunity of Thymidine Kinase-Deleted Vaccinia Virus Guang9 Strain

Overview

Journal Onco Targets Ther

Publisher Dove Medical Press

Specialty Oncology

Date 2020 Aug 18

PMID 32801778

Citations 1

Authors

Yuedi Ding

Jun Fan

Lili Deng

Ying Peng

Bin Zhou

Biao Huang

Affiliations

Soon will be listed here.

Abstract

Purpose: Oncolytic viruses are emerging as promising options for clinical cancer treatment due to their inherent ability of tumor tropism and oncolytic property. Aside from tumor lysis, oncolytic viruses can induce host immune responses against tumor cells and may thus be viewed as a form of immunotherapy.

Methods: The attenuated vaccinia VG9-Luc, which originated from Chinese vaccinia Tian Tan strain, was constructed to express firefly luciferase for bioluminescence imaging and to disrupt the thymidine kinase gene for promoting tumor specificity. An in vivo bioluminescence imaging was performed to observe the virus distribution in live mice. The titers of neutralizing antiviral and antitumor antibodies in plasma were determined by time-resolved fluoroimmunoassay.

Results: Except BALB/c mice treated with intravenous virus injection, all immunocompromised and immunocompetent mice showed obvious tumor targeting ability of vaccinia VG9-Luc. Besides, host immune response activated by vaccinia VG9-Luc showed the production of antiviral and antitumor antibodies, the process of which was similar between intravenous and intratumoral viral delivery systems. The results indicated that virus infection promoted tumor-specific immunity by increasing the production of antitumor antibodies. Moreover, virus reinjection was performed and a more rapid viral clearance was observed in immunocompetent mice compared with first virus infection.

Conclusion: The thymidine kinase-deleted vaccinia Guang9 strain, which has the properties of tumor specificity and antitumor immunity, is a promising candidate vector for cancer therapy.

Citing Articles

Combined anti-tumor efficacy of somatostatin fusion protein and vaccinia virus on tumor cells with high expression of somatostatin receptors.

Fan J, Deng L, Peng Y, Ding Y Sci Rep. 2022; 12(1):16885.

PMID: 36207478 PMC: 9547013. DOI: 10.1038/s41598-022-21506-8.

References

Dai P, Wang W, Yang N, Serna-Tamayo C, Ricca J, Zamarin D . Intratumoral delivery of inactivated modified vaccinia virus Ankara (iMVA) induces systemic antitumor immunity via STING and Batf3-dependent dendritic cells. Sci Immunol. 2017; 2(11). PMC: 5559204. DOI: 10.1126/sciimmunol.aal1713. View

Guo Z, Lu B, Guo Z, Giehl E, Feist M, Dai E . Vaccinia virus-mediated cancer immunotherapy: cancer vaccines and oncolytics. J Immunother Cancer. 2019; 7(1):6. PMC: 6325819. DOI: 10.1186/s40425-018-0495-7. View

Huang B, Tao W, Shi J, Tang L, Jin J . Determination of ochratoxin A by polyclonal antibodies based sensitive time-resolved fluoroimmunoassay. Arch Toxicol. 2006; 80(8):481-5. DOI: 10.1007/s00204-006-0112-2. View

Hwang T, Moon A, Burke J, Ribas A, Stephenson J, Breitbach C . A mechanistic proof-of-concept clinical trial with JX-594, a targeted multi-mechanistic oncolytic poxvirus, in patients with metastatic melanoma. Mol Ther. 2011; 19(10):1913-22. PMC: 3188739. DOI: 10.1038/mt.2011.132. View

Raki M, Sarkioja M, Escutenaire S, Kangasniemi L, Haavisto E, Kanerva A . Switching the fiber knob of oncolytic adenoviruses to avoid neutralizing antibodies in human cancer patients. J Gene Med. 2011; 13(5):253-61. DOI: 10.1002/jgm.1565. View

Argnani R, Marconi P, Volpi I, Bolanos E, Carro E, Ried C . Characterization of herpes simplex virus 1 strains as platforms for the development of oncolytic viruses against liver cancer. Liver Int. 2011; 31(10):1542-53. DOI: 10.1111/j.1478-3231.2011.02628.x. View

Thorne S, Hwang T, OGorman W, Bartlett D, Sei S, Kanji F . Rational strain selection and engineering creates a broad-spectrum, systemically effective oncolytic poxvirus, JX-963. J Clin Invest. 2007; 117(11):3350-8. PMC: 2040321. DOI: 10.1172/JCI32727. View

Kaufman H, Kohlhapp F, Zloza A . Oncolytic viruses: a new class of immunotherapy drugs. Nat Rev Drug Discov. 2015; 14(9):642-62. PMC: 7097180. DOI: 10.1038/nrd4663. View

Zhu R, Liu Q, Huang W, Yu Y, Wang Y . Comparison of the replication characteristics of vaccinia virus strains Guang 9 and Tian Tan in vivo and in vitro. Arch Virol. 2014; 159(10):2587-96. DOI: 10.1007/s00705-014-2079-2. View

10.

McCart J, Ward J, Lee J, Hu Y, Alexander H, Libutti S . Systemic cancer therapy with a tumor-selective vaccinia virus mutant lacking thymidine kinase and vaccinia growth factor genes. Cancer Res. 2001; 61(24):8751-7. View

11.

Deng L, Fan J, Guo M, Huang B . Oncolytic and immunologic cancer therapy with GM-CSF-armed vaccinia virus of Tian Tan strain Guang9. Cancer Lett. 2016; 372(2):251-7. DOI: 10.1016/j.canlet.2016.01.025. View

12.

Pease D, Kratzke R . Oncolytic Viral Therapy for Mesothelioma. Front Oncol. 2017; 7:179. PMC: 5573749. DOI: 10.3389/fonc.2017.00179. View

13.

Wakimoto H, Johnson P, Knipe D, Chiocca E . Effects of innate immunity on herpes simplex virus and its ability to kill tumor cells. Gene Ther. 2003; 10(11):983-90. DOI: 10.1038/sj.gt.3302038. View

14.

Breitbach C, Burke J, Jonker D, Stephenson J, Haas A, Chow L . Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans. Nature. 2011; 477(7362):99-102. DOI: 10.1038/nature10358. View

15.

Lee J, Roh M, Lee Y, Kim M, Han J, Park B . Oncolytic and immunostimulatory efficacy of a targeted oncolytic poxvirus expressing human GM-CSF following intravenous administration in a rabbit tumor model. Cancer Gene Ther. 2009; 17(2):73-9. PMC: 2834359. DOI: 10.1038/cgt.2009.50. View

16.

Heo J, Reid T, Ruo L, Breitbach C, Rose S, Bloomston M . Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer. Nat Med. 2013; 19(3):329-36. PMC: 4268543. DOI: 10.1038/nm.3089. View

17.

Liu T, Galanis E, Kirn D . Clinical trial results with oncolytic virotherapy: a century of promise, a decade of progress. Nat Clin Pract Oncol. 2007; 4(2):101-17. DOI: 10.1038/ncponc0736. View

18.

Friedman A, Tian J, Fulci G, Chiocca E, Wang J . Glioma virotherapy: effects of innate immune suppression and increased viral replication capacity. Cancer Res. 2006; 66(4):2314-9. DOI: 10.1158/0008-5472.CAN-05-2661. View

19.

Breitbach C, Moon A, Burke J, Hwang T, Kirn D . A Phase 2, Open-Label, Randomized Study of Pexa-Vec (JX-594) Administered by Intratumoral Injection in Patients with Unresectable Primary Hepatocellular Carcinoma. Methods Mol Biol. 2015; 1317:343-57. DOI: 10.1007/978-1-4939-2727-2_19. View

20.

Gkretsi V, Stylianopoulos T . Cell Adhesion and Matrix Stiffness: Coordinating Cancer Cell Invasion and Metastasis. Front Oncol. 2018; 8:145. PMC: 5945811. DOI: 10.3389/fonc.2018.00145. View