Antitumor immunity enhancement through Newcastle viral oncolysate in mice model: A promising method to treat tumors

Amir Sasan Mozaffari Nejad; Fatemeh Fotouhi; Parvaneh Mehrbod; Mohammad Yousef Alikhani

doi:10.1016/j.sjbs.2021.06.043

Antitumor immunity enhancement through Newcastle viral oncolysate in mice model: A promising method to treat tumors

Saudi J Biol Sci. 2021 Oct;28(10):5833-5840. doi: 10.1016/j.sjbs.2021.06.043. Epub 2021 Jun 18.

Authors

Amir Sasan Mozaffari Nejad¹, Fatemeh Fotouhi², Parvaneh Mehrbod², Mohammad Yousef Alikhani³

Affiliations

¹ Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
² Influenza and Respiratory Viruses Department, Pasteur Institute of Iran, Tehran, Iran.
³ Department of Microbiology, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

Abstract

A Newcastle disease virus (NDV) oncolysate has been established as a unique and effective immune-stimulatory root for tumor treatment. Thus, the aim of the current study was to investigate the effects of intratumoral administration of NDV oncolysate on immune response and tumor regression of C57BL/6 mouse model of human papillomavirus (HPV) related transplanted with TC-1 syngeneic cancer cells. To further investigate the mechanism underlying the antitumor response, cytolytic and lymphocyte proliferation responses in splenocytes were measured using lactate dehydrogenase (LDH) release and MTT assays, respectively. In this regard, levels of IL-10, IFN-γ, and IL-4 were measured using ELISA after re-stimulation. The immune responses efficacy was evaluated by in vivo tumor regression assay. The results showed that immunization with the different titers of NDV lysate significantly reduced tumor volume in comparison with a combination of virus lysate and tumor cell lysate. Also, virus lysate could significantly enhance cytotoxic T lymphocyte production and lymphocyte proliferation rates versus tumor cell lysate. Also, our major findings are that the peritumorally injection of NDV oncolysate effectively induces antitumor immune responses through increased levels of IL-4, IFN-γ, and reduction of IL-10. These results indicate that this treatment is a specific, active immune mechanism stimulator, and may prove to be a useful therapeutic for a treatment against cervical cancers and merits further investigation.

Keywords: DAMP, Danger-associated molecular pattern; ELISA, Enzyme-Linked Immunosorbent Assay; FBS, Fetal bovine serum; FDA, Food and drug administration; HB1, Hitchner B1; HPV, Human papillomavirus; Human papillomavirus; LDH, Lactate dehydrogenase; MOI, Multiplicity of infection; NDV, Newcastle disease virus; Newcastle disease virus; OVs, Oncolytic viruses; Oncolysate; Oncolytic; PBS, Phosphate-buffered saline; RPMI, Roswell park memorial institute; T-Vec, Talimogene laherparepvec; Tumor microenvironment; UVB, Ultraviolet B; VO, Viral oncolysate.