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Synergistic effect of programmed cell death protein 1 blockade and secondary lymphoid tissue chemokine in the induction of anti-tumor immunity by a therapeutic cancer vaccine

Moeini, S. and Saeidi, M. and Fotouhi, F. and Mondanizadeh, M. and Shirian, S. and Mohebi, A. and Gorji, A. and Ghaemi, A. (2017) Synergistic effect of programmed cell death protein 1 blockade and secondary lymphoid tissue chemokine in the induction of anti-tumor immunity by a therapeutic cancer vaccine. Archives of Virology, 162 (2). pp. 333-346.

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Abstract

The use of DNA vaccines has become an attractive approach for generating antigen-specific cytotoxic CD8+ T lymphocytes (CTLs), which can mediate protective antitumor immunity. The potency of DNA vaccines encoding weakly immunogenic tumor-associated antigens (TAAs) can be improved by using an adjuvant injected together with checkpoint antibodies. In the current study, we evaluated whether the therapeutic effects of a DNA vaccine encoding human papilloma virus type 16 (HPV-16) E7 can be enhanced by combined application of an immune checkpoint blockade directed against the programmed death-1 (PD-1) pathway and secondary lymphoid tissue chemokine (SLC) also known as CCL21 adjuvant, in a mouse cervical cancer model. The therapeutic effects of the DNA vaccine in combination with CCL21 adjuvant plus PD-1 blockade was evaluated using a tumor growth curve. To further investigate the mechanism underlying the antitumor response, cytolytic and lymphocyte proliferation responses in splenocytes were measured using non-radioactive cytotoxicity and MTT assays, respectively. Vascular endothelial growth factor (VEGF) and IL-10 expression in the tumor and the levels of IFN-γ and IL-4 in supernatants of spleno-lymphocyte cultures were measured using ELISA. The immune efficacy was evaluated by in vivo tumor regression assay. The results showed that vaccination with a DNA vaccine in combination with the CCL21 adjuvant plus PD-1 blockade greatly enhanced cytotoxic T lymphocyte production and lymphocyte proliferation rates and greatly inhibited tumor progression. Moreover, the vaccine in combination with adjuvant and blockade significantly reduced intratumoral VEGF, IL-10 and splenic IL-4 but induced the expression of splenic IFN-γ. This formulation could be an effective candidate for a vaccine against cervical cancers and merits further investigation. © 2016, Springer-Verlag Wien.

Item Type: Article
Additional Information: cited By 0
Uncontrolled Keywords: cancer vaccine; DNA vaccine; gamma interferon; IL10 protein, mouse; immunological adjuvant; interleukin 10; interleukin 4; neutralizing antibody; Pdcd1 protein, mouse; programmed death 1 receptor; protein E7; secondary lymphoid tissue chemokine; tumor antigen; vascular endothelial growth factor A, mouse; vasculotropin A, animal; antagonists and inhibitors; CD8+ T lymphocyte; chemistry; disease model; drug effects; female; gene expression regulation; genetics; human; Human papillomavirus type 16; immunology; mouse; Papillomavirus Infections; pathology; plasmid; signal transduction; spleen; Uterine Cervical Neoplasms; virology, Adjuvants, Immunologic; Animals; Antibodies, Neutralizing; Antigens, Neoplasm; Cancer Vaccines; CD8-Positive T-Lymphocytes; Chemokine CCL21; Disease Models, Animal; Female; Gene Expression Regulation, Neoplastic; Human papillomavirus 16; Humans; Interferon-gamma; Interleukin-10; Interleukin-4; Mice; Papillomavirus E7 Proteins; Papillomavirus Infections; Plasmids; Programmed Cell Death 1 Receptor; Signal Transduction; Spleen; Uterine Cervical Neoplasms; Vaccines, DNA; Vascular Endothelial Growth Factor A
Subjects: مقالات نمایه شده محققین دانشگاه در سایت ,Web of Science ,Scopus
Divisions: UNSPECIFIED
Depositing User: GOUMS
Date Deposited: 18 Jun 2017 16:56
Last Modified: 18 Jun 2017 16:56
URI: http://eprints.goums.ac.ir/id/eprint/5102

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