Research Article

Department of Biochemistry & Molecular Biology, School of Basic Medicine Sciences, Guangxi Colleges & Universities Key Laboratory of Biological Molecular Medicine Research, Guangxi Medical University, Nanning, Guangxi, 530021, PR China

‡Authors contributed equally

Shunli Guo‡

‡Authors contributed equally

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Yisen Feng

National Center for International Research of Biological Targeting Diagnosis & Therapy, Guangxi Medical University, Nanning, Guangxi, China

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Dandan Wu

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Yapei Li

Department of Health Management, the Third Xiangya Hospital, Central South University, Changsha, China

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Zhouyangfan Peng

*Author for correspondence:

E-mail Address: pengzyf@csu.edu.cn

Department of Health Management, the Third Xiangya Hospital, Central South University, Changsha, China

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Sufang Zhou

**Author for correspondence:

E-mail Address: zsf200000@163.com

Key Laboratory of Early Prevention & Treatment for Regional High Frequency Tumor (Gaungxi Medical University), Ministry of Education, Nanning, Guangxi, China

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Published Online:3 Mar 2023https://doi.org/10.2217/fvl-2022-0183

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Abstract

Aim: To construct and rescue a recombinant Newcastle disease virus that can express IP10 protein and evaluate its targeted killing effect on liver cancer in vivo and in vitro. Materials & methods: Fluorescence quantitative PCR, western blot and ELISA were used to detect the expression and secretion of IP10 in cells. The H22 mouse liver cancer cells were used to establish subcutaneous tumor-bearing mice experimental animal tumor models, and the tumor growth of mice in each group was observed while receiving treatment with rLasota. Results: The recombinant Newcastle disease virus was successfully constructed and can kill tumor cells successfully. Conclusion: The rLasota-IP10-IRES-EGFP achieves antitumor effects by killing hepatocellular carcinoma cells, enhancing T-lymphocyte infiltration in tumor tissues and inhibiting neovascularization.

Plain language summary

What does this study talk about?

This is a basic research article about Recombinant Newcastle disease virus. Given the excellent antitumor effect of IP10 protein and the good oncolytic effect of Newcastle disease virus, we expect to add the two effects to produce chemical action to kill tumor cells.

What is the result of this study?

We have done experiments in vivo and in vitro, which show that the antitumor effect is very good. Our research shows that the sum of the two results is greater than the single, which may provide new ideas for future clinical antitumor research.

Tweetable abstract

Recombinant Newcastle disease virus rLasota-IP10-IRES-EGFP has been constructed and rescued. The rLasota-IP10-IRES-EGFP achieves antitumor effects by killing hepatocellular carcinoma cells, enhancing T-lymphocyte infiltration in tumor tissues and inhibiting neovascularization.

Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

References

1. Huang DQ, El-Serag HB, Loomba R. Global epidemiology of NAFLD-related HCC: trends, predictions, risk factors and prevention. Nat. Rev. Gastroenterol. Hepatol. 10(1038), 1–16 (2020).
Google Scholar
2. Pinato DJ, Mauri FA, Spina P et al. Clinical implications of heterogeneity in PD-L1 immunohistochemical detection in hepatocellular carcinoma: the Blueprint-HCC study. Br. J. Cancer 120(11), 1033–1036 (2019).
MedlineGoogle Scholar
3. Lei GL, Wang LP, Dong SH et al. A recombinant influenza virus with a CTLA4-specific scFv inhibits tumor growth in a mouse model. Cell Biol. Int. 45(6), 1202–1210 (2021). • Recombinant influenza viruses can produce certain antitumor effects. As an oncolytic virus, the effect of Newcastle disease virus may be better.
Medline CASGoogle Scholar
4. Lathwal A, Kumar R, Raghava GPS. OvirusTdb: a database of oncolytic viruses for the advancement of therapeutics in cancer. Virology 548, 109–116 (2020).
Medline CASGoogle Scholar
5. Sinkovics JG, Horvath JC. Newcastle disease virus (NDV): brief history of its oncolytic strains. J. Clin. Virol. 16(1), 1–15 (2000).
Medline CASGoogle Scholar
6. Pan Z, He J, Rasoul LM et al. Identification of optimal insertion site in recombinant newcastle disease virus (rNDV) vector expressing foreign gene to enhance its anti-tumor effect. PLOS ONE 11(10), e0164723 (2016). •• Some people have begun to study the antitumor effect of recombinant Newcastle disease virus, but the antitumor effect of IP10 has also been receiving much attention.
MedlineGoogle Scholar
7. Muscolini M, Tassone E, Hiscott J. Oncolytic immunotherapy: can't start a fire without a spark. Cytokine Growth Factor Rev. 11(56), 94–101 (2020).
Google Scholar
8. Elankumaran S, Chavan V, Qiao D et al. Type I interferon-sensitive recombinant Newcastle disease virus for oncolytic virotherapy. J. Virol. 84(8), 3835–3844 (2010).
Medline CASGoogle Scholar
9. Fiola C, Peeters B, Fournier P et al. Tumor selective replication of Newcastle disease virus: association with defects of tumor cells in antiviral defence. Int. J. Cancer 119(2), 328–338 (2006).
Medline CASGoogle Scholar
10. Fournier P, Wilden H, Schirrmacher V. Importance of retinoic acid-inducible gene I and of receptor for type I interferon for cellular resistance to infection by Newcastle disease virus. Int. J. Oncol. 40(1), 287–298 (2012).
Medline CASGoogle Scholar
11. Reichard KW, Lorence RM, Cascino CJ et al. Newcastle disease virus selectively kills human tumor cells. J. Surg. Res. 52(5), 448–453 (1992).
Medline CASGoogle Scholar
12. Termeer CC, Schirrmacher V, Brocker EB et al. Newcastle disease virus infection induces B7-1/B7-2-independent T-cell costimulatory activity in human melanoma cells. Cancer Gene Ther. 7(2), 316–323 (2000).
Medline CASGoogle Scholar
13. Batliwalla FM, Bateman BA, Serrano D et al. A 15-year follow-up of AJCC stage III malignant melanoma patients treated postsurgically with Newcastle disease virus (NDV) oncolysate and determination of alterations in the CD8 T cell repertoire. Mol. Med. 4(12), 783–794 (1998).
Medline CASGoogle Scholar
14. Loetscher M, Gerber B, Loetscher P et al. Chemokine receptor specific for IP10 and mig: structure, function, and expression in activated T-lymphocytes. J. Exp. Med. 184(3), 963–969 (1996).
Medline CASGoogle Scholar
15. Arenberg DA, Kunkel SL, Polverini PJ et al. Interferon-gamma-inducible protein 10 (IP-10) is an angiostatic factor that inhibits human non-small cell lung cancer (NSCLC) tumorigenesis and spontaneous metastases. J. Exp. Med. 184(3), 981–992 (1996).
Medline CASGoogle Scholar
16. Lin C, Yan H, Yang J et al. Combination of DESI2 and IP10 gene therapy significantly improves therapeutic efficacy against murine carcinoma. Oncotarget 8(34), 56281–56295 (2017 May 5).
MedlineGoogle Scholar
17. Damjanovska S, Alao H, Zebrowski E et al. During HCV DAA therapy plasma Mip1B, IP10, and miRNA profile are distinctly associated with subsequent diagnosis of hepatocellular carcinoma: a pilot study. Biology (Basel) 11(9), 1262 (2022).
Medline CASGoogle Scholar
18. Calvo-Pinilla E, Marin-Lopez A, Utrilla-Trigo S et al. Reverse genetics approaches: a novel strategy for African horse sickness virus vaccine design. Curr. Opin. Virol. 10(44), 49–56 (2020).
Google Scholar
19. Zamarin D, Palese P. Oncolytic Newcastle disease virus for cancer therapy: old challenges and new directions. Fut. Microbiol. 7(3), 347–367 (2012).
CASGoogle Scholar
20. Bai FL, Tian H, Yu YH et al. TNF-related apoptosis-inducing ligand delivered by rNDV is a novel agent for cancer gene therapy. Technol. Cancer Res. Treat. 14(6), 737–746 (2015).
Medline CASGoogle Scholar
21. Wu Y, He J, An Y et al. Recombinant Newcastle disease virus (NDV/Anh-IL-2) expressing human IL-2 as a potential candidate for suppresses growth of hepatoma therapy. J. Pharmacol. Sci. 132(1), 24–30 (2016).
Medline CASGoogle Scholar
22. Pinato DJ, Guerra N, Fessas P et al. Immune-based therapies for hepatocellular carcinoma. Oncogene 39(18), 3620–3637 (2020).
Medline CASGoogle Scholar
23. Lorence RM, Katubig BB, Reichard KW et al. Complete regression of human fibrosarcoma xenografts after local Newcastle disease virus therapy. Cancer Res. 54(23), 6017–6021 (1994).
Medline CASGoogle Scholar
24. Lorence RM, Reichard KW, Katubig BB et al. Complete regression of human neuroblastoma xenografts in athymic mice after local Newcastle disease virus therapy. J. Natl Cancer Inst. 86(16), 1228–1233 (1994).
Medline CASGoogle Scholar
25. Lorence RM, Roberts MS, O'Neil JD et al. Phase 1 clinical experience using intravenous administration of PV701, an oncolytic Newcastle disease virus. Curr. Cancer Drug Targets 7(2), 157–167 (2007).
Medline CASGoogle Scholar
26. Laurie SA, Bell JC, Atkins HL et al. A phase 1 clinical study of intravenous administration of PV701, an oncolytic virus, using two-step desensitization. Clin. Cancer Res. 12(8), 2555–2562 (2006).
Medline CASGoogle Scholar
27. Nakaya T, Cros J, Park MS et al. Recombinant Newcastle disease virus as a vaccine vector. J. Virol. 75(23), 11868–11873 (2001).
Medline CASGoogle Scholar
28. DiNapoli JM, Yang L, Samal SK et al. Respiratory tract immunization of non-human primates with a Newcastle disease virus-vectored vaccine candidate against Ebola virus elicits a neutralizing antibody response. Vaccine 29(1), 17–25 (2010).
Medline CASGoogle Scholar
29. Vagnozzi A, Garcia M, Riblet SM et al. Protection induced by infectious laryngotracheitis virus vaccines alone and combined with Newcastle disease virus and/or infectious bronchitis virus vaccines. Avian. Dis. 54(4), 1210–1219 (2010).
MedlineGoogle Scholar
30. Khattar SK, Samal S, Devico AL et al. Newcastle disease virus expressing human immunodeficiency virus type 1 envelope glycoprotein induces strong mucosal and serum antibody responses in Guinea pigs. J. Virol. 85(20), 10529–10541 (2011).
Medline CASGoogle Scholar
31. Takano S, Ishikawa E, Matsuda M et al. Interferon-beta inhibits glioma angiogenesis through downregulation of vascular endothelial growth factor and upregulation of interferon inducible protein 10. Int. J Oncol. 45(5), 1837–1846 (2014).
Medline CASGoogle Scholar
32. DiNapoli JM, Kotelkin A, Yang L et al. Newcastle disease virus, a host range-restricted virus, as a vaccine vector for intranasal immunization against emerging pathogens. Proc. Natl Acad. Sci. 104(23), 9788–9793 (2007).
Medline CASGoogle Scholar
33. Nagai Y. Paramyxovirus replication and pathogenesis. Reverse genetics transforms understanding. Rev. Med. Virol. 9(2), 83–99 (1999).
Medline CASGoogle Scholar
34. Huang Z, Krishnamurthy S, Panda A et al. High-level expression of a foreign gene from the most 3′-proximal locus of a recombinant Newcastle disease virus. J. Gen. Virol. 82(7), 1729–1736 (2001).
Medline CASGoogle Scholar

Vol. 18, No. 3

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History

Received 30 November 2022

Accepted 7 February 2023

Published online 3 March 2023

Published in print February 2023

Information

Keywords

Author contributions

D Yang and S Guo were involved in drafting the manuscript, acquisition and analysis of data. Y Feng and D Wu contributed to the conception and design of the study and the acquisition of the data. Y Li and Z Peng were responsible for analysis and interpretation of the data. S Zhou was for responsible for conceived and directed the project, and approval of the final version to be published. All authors read and approved the final manuscript.

Acknowledgments

The authors would like to thank G Jinying (Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences) for Reverse genetics advice and pBRN-PmeI, pBS-NP, pBS-P and pBS-L plasmids.

Financial & competing interests disclosure

This work was funded by the National Natural Science Foundation of China (NSFC) project (no. 82273103, 81572994 and 82100444); Key Laboratory of the Ministry of Education Project for Early Prevention and Treatment of Regional High-risk Tumors/Key Laboratory of Guangxi (GKE-ZZ202007 and GKE-ZZ202127); National Science and Technology Basic Resources Investigation Special Project (2017FY101200-3). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.

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Recombinant Newcastle disease virus kills liver cancer in vitro and in vivo

Abstract

Plain language summary

What does this study talk about?

What is the result of this study?

Tweetable abstract

References