NDLI: 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

Content Provider	Springer Nature Link
Author	Moeini, Soheila Saeidi, Mohsen Fotouhi, Fatemeh Mondanizadeh, Mahdieh Shirian, Sadegh Mohebi, Alireza Gorji, Ali Ghaemi, Amir
Copyright Year	2016
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.
Starting Page	333
Ending Page	346
Page Count	14
File Format	PDF
ISSN	03048608
Journal	Archives of Virology
Volume Number	162
Issue Number	2
e-ISSN	14328798
Language	English
Publisher	Springer Vienna
Publisher Date	2016-10-03
Publisher Place	Vienna
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Virology Medical Microbiology Infectious Diseases
Content Type	Text
Resource Type	Article
Subject	Virology Medicine

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Erratum to: 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

Erratum to: 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

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