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Non-replicating Newcastle Disease Virus as an adjuvant for DNA vaccine enhances antitumor efficacy through the induction of TRAIL and granzyme B expression

Mohebbi, A. and Ebrahimzadeh, M.S. and Baghban Rahimi, S. and Saeidi, M. and Tabarraei, A. and Mohebbi, S.R. and Shirian, S. and Gorji, A. and Ghaemi, A. (2019) Non-replicating Newcastle Disease Virus as an adjuvant for DNA vaccine enhances antitumor efficacy through the induction of TRAIL and granzyme B expression. Virus Research, 261. pp. 72-80.

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Abstract

The potential of non-replicating Newcastle Disease Virus (NDV) as an adjuvant for DNA vaccination remains to be elucidated. To assess the therapeutic effects of DNA vaccine (HPV-16 E7 gene) adjuvanted with NDV, female C57/BL6 mice were inoculated with murine TC-1 cells of human papillomavirus (HPV)-related carcinoma, expressing human papillomavirus 16 (HPV-16) E6/E7 antigens, and immunized with DNA vaccine alone or pretreated with NDV. One week after third immunization, Cytotoxic T lymphocytes (CTLs), splenocyte proliferation, cytokine balance (IFN-γ IL-4 and IL-12 secretions) and intratumoral expression of cytotoxicity related proteins in tumor lysates were investigated. The results showed that treatment with non-replicating NDV prior to DNA vaccine induced tumor-specific cytolytic and splenocyte proliferation responses. The levels of cytokines IL-12, IL-4 and IFN�γ after treating with combined E7-DNA -non-replicating NDV (NDV-DNA Vaccine) were significantly higher than those of control groups. The intratumoral granzyme B and Tumor Necrosis Factor Related Apoptosis Inducing Ligand (TRAIL)-mediated apoptosis was also significantly increased. Tumor therapeutic experiments showed that the NDV pretreatment could reduce the tumor progression of established E7-expressing TC-tumors. Taken together these data suggest that the significant antitumor responses evidenced during treatment with non-replicating NDV prior to DNA vaccine are due, in part, to strong E7-induced cellular immunity and enhanced expression of cytotoxicity related proteins in the tumor microenvironment. These observations indicated the potential of non-replicating NDV as an adjuvant for enhancing therapeutic DNA vaccines -induced immunity and antitumor responses. © 2018 Elsevier B.V.

Item Type: Article
Additional Information: cited By 0
Uncontrolled Keywords: DNA vaccine; gamma interferon; granzyme B; interleukin 12; interleukin 4; oncolytic virus; tumor necrosis factor related apoptosis inducing ligand; virus antigen; cancer vaccine; cytokine; DNA vaccine; granzyme; immunological adjuvant; live vaccine; oncoprotein; Tnfsf10 protein, mouse; tumor necrosis factor related apoptosis inducing ligand; virus vaccine, adaptive immunity; adjuvant therapy; animal cell; animal experiment; animal model; antineoplastic activity; Article; cancer immunization; cancer immunotherapy; cellular immunity; controlled study; cytokine release; cytotoxicity; drug efficacy; female; Human papillomavirus type 16; lymphocyte proliferation; mouse; Newcastle disease virus; nonhuman; oncolytic virotherapy; priority journal; protein expression; spleen cell; tumor growth; tumor microenvironment; animal; C57BL mouse; cell proliferation; cytotoxic T lymphocyte; disease model; genetics; immunology; lung tumor; metabolism; treatment outcome; tumor cell line, Adjuvants, Immunologic; Animals; Cancer Vaccines; Cell Line, Tumor; Cell Proliferation; Cytokines; Disease Models, Animal; Female; Granzymes; Human papillomavirus 16; Lung Neoplasms; Mice, Inbred C57BL; Oncogene Proteins, Viral; T-Lymphocytes, Cytotoxic; TNF-Related Apoptosis-Inducing Ligand; Treatment Outcome; Vaccines, Attenuated; Vaccines, DNA; Viral Vaccines
Subjects: آسیب شناسی QZ
میکروب شناسی وایمنی شناسی QW
مقالات نمایه شده محققین دانشگاه در سایت ,Web of Science ,Scopus
موارد کلی
Divisions: معاونت تحقیقات و فناوری
Depositing User: GOUMS
Date Deposited: 14 Apr 2019 04:11
Last Modified: 14 Apr 2019 04:11
URI: http://eprints.goums.ac.ir/id/eprint/9902

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