Newcastle Disease Virus Virotherapy: Unveiling Oncolytic Efficacy and Immunomodulation

Overview

Journal Biomedicines

Specialty Biomedical Engineering

Date 2024 Jul 27

PMID 39062070

Authors

Kawther A Zaher

Jehan S Alrahimi

Fatemah S Basingab

Alia M Aldahlawi

Affiliations

Soon will be listed here.

Abstract

Background: This study aims to evaluate the oncolytic potential of Newcastle disease virus (NDV) against colon cancer and explore the immune response associated with its therapeutic effects.

Methods: NDV was tested for its oncolytic potential in colon cancer cell lines using MTT assays and apoptosis assessments. Tumor-induced mice were treated with NDV, tumor cell lysate (TCL), or a combination of both. After the euthanasia of murine subjects, an assessment of oncolytic efficacy was performed through flow cytometry analysis of murine blood and tumor tissue, targeting CD83, CD86, CD8, and CD4. An ELISA was also performed to examine interferon-gamma levels, interleukin-4 levels, interleukin-12 levels, and interleukin-10 levels in serum and spleen homogenate.

Results: Cell viability was low in HCT116 and HT-29, indicating a cytotoxic effect in the MTT assay. NDV+TCL recorded the highest rate of cell death (56.72%). NDV+TCL had accelerated cell death after 48 h, reaching 58.4%. The flow cytometry analysis of the blood and tumor of mice with induced tumor treated with combined treatment revealed elevated levels of CD83, CD86, CD8, and CD4 (76.3, 66.9, 83.7, and 14.4%, respectively). The ELISA levels of IFN-γ, IL-4, and IL-12 in serum and the spleen homogenate were elevated (107.6 ± 9.25 pg/mL). In contrast, the expression of IL-10 was significantly reduced (1 ± 0.79).

References

Harrington K, Freeman D, Kelly B, Harper J, Soria J . Optimizing oncolytic virotherapy in cancer treatment. Nat Rev Drug Discov. 2019; 18(9):689-706. DOI: 10.1038/s41573-019-0029-0. View

Cespedes M, Espina C, Garcia-Cabezas M, Trias M, Boluda A, Gomez Del Pulgar M . Orthotopic microinjection of human colon cancer cells in nude mice induces tumor foci in all clinically relevant metastatic sites. Am J Pathol. 2007; 170(3):1077-85. PMC: 1864873. DOI: 10.2353/ajpath.2007.060773. View

Yaacov B, Eliahoo E, Elihaoo E, Lazar I, Ben-Shlomo M, Greenbaum I . Selective oncolytic effect of an attenuated Newcastle disease virus (NDV-HUJ) in lung tumors. Cancer Gene Ther. 2008; 15(12):795-807. DOI: 10.1038/cgt.2008.31. View

Breitbach C, Lichty B, Bell J . Oncolytic Viruses: Therapeutics With an Identity Crisis. EBioMedicine. 2016; 9:31-36. PMC: 4972563. DOI: 10.1016/j.ebiom.2016.06.046. View

Sinkovics J, Horvath J . Newcastle disease virus (NDV): brief history of its oncolytic strains. J Clin Virol. 2000; 16(1):1-15. DOI: 10.1016/s1386-6532(99)00072-4. View

Tau G, Rothman P . Biologic functions of the IFN-gamma receptors. Allergy. 2000; 54(12):1233-51. PMC: 4154595. DOI: 10.1034/j.1398-9995.1999.00099.x. View

Schirrmacher V, Fournier P . Newcastle disease virus: a promising vector for viral therapy, immune therapy, and gene therapy of cancer. Methods Mol Biol. 2009; 542:565-605. PMC: 7122391. DOI: 10.1007/978-1-59745-561-9_30. View

Russell S, Peng K, Bell J . Oncolytic virotherapy. Nat Biotechnol. 2012; 30(7):658-70. PMC: 3888062. DOI: 10.1038/nbt.2287. View

Ye T, Jiang K, Wei L, Barr M, Xu Q, Zhang G . Oncolytic Newcastle disease virus induces autophagy-dependent immunogenic cell death in lung cancer cells. Am J Cancer Res. 2018; 8(8):1514-1527. PMC: 6129498. View

10.

Freeman A, Zakay-Rones Z, Gomori J, Linetsky E, Rasooly L, Greenbaum E . Phase I/II trial of intravenous NDV-HUJ oncolytic virus in recurrent glioblastoma multiforme. Mol Ther. 2005; 13(1):221-8. DOI: 10.1016/j.ymthe.2005.08.016. View

11.

Liang Y, Tian W, Huang J, Gao L, Fan X . MicroRNA-204 plays a role as a tumor suppressor in Newcastle disease virus-induced oncolysis in lung cancer A549 cells. Oncol Lett. 2021; 21(6):482. PMC: 8100940. DOI: 10.3892/ol.2021.12743. View

12.

Meng F, Cao Y, Su H, Liu T, Tian L, Zhang Y . Newcastle disease virus expressing an angiogenic inhibitor exerts an enhanced therapeutic efficacy in colon cancer model. PLoS One. 2022; 17(4):e0264896. PMC: 8982889. DOI: 10.1371/journal.pone.0264896. View

13.

Cattaneo R, Miest T, Shashkova E, Barry M . Reprogrammed viruses as cancer therapeutics: targeted, armed and shielded. Nat Rev Microbiol. 2008; 6(7):529-40. PMC: 3947522. DOI: 10.1038/nrmicro1927. View

14.

Bashyam H . Interleukin-12: a master regulator. J Exp Med. 2007; 204(5):969. PMC: 2118588. DOI: 10.1084/jem.2045fta. View

15.

Von Hoegen P, Zawatzky R, Schirrmacher V . Modification of tumor cells by a low dose of Newcastle disease virus. III. Potentiation of tumor-specific cytolytic T cell activity via induction of interferon-alpha/beta. Cell Immunol. 1990; 126(1):80-90. DOI: 10.1016/0008-8749(90)90302-8. View

16.

Wang X, Shao X, Gu L, Jiang K, Wang S, Chen J . Targeting STAT3 enhances NDV-induced immunogenic cell death in prostate cancer cells. J Cell Mol Med. 2020; 24(7):4286-4297. PMC: 7171322. DOI: 10.1111/jcmm.15089. View

17.

Meng Q, He J, Zhong L, Zhao Y . Advances in the Study of Antitumour Immunotherapy for Newcastle Disease Virus. Int J Med Sci. 2021; 18(11):2294-2302. PMC: 8100649. DOI: 10.7150/ijms.59185. View

18.

Nascimento-Goncalves E, Mendes B, Silva-Reis R, Faustino-Rocha A, Gama A, Oliveira P . Animal Models of Colorectal Cancer: From Spontaneous to Genetically Engineered Models and Their Applications. Vet Sci. 2021; 8(4). PMC: 8067250. DOI: 10.3390/vetsci8040059. View

19.

Pikor L, Bell J, Diallo J . Oncolytic Viruses: Exploiting Cancer's Deal with the Devil. Trends Cancer. 2017; 1(4):266-277. DOI: 10.1016/j.trecan.2015.10.004. View

20.

Hu L, Sun S, Wang T, Li Y, Jiang K, Lin G . Oncolytic newcastle disease virus triggers cell death of lung cancer spheroids and is enhanced by pharmacological inhibition of autophagy. Am J Cancer Res. 2016; 5(12):3612-23. PMC: 4731635. View