Oncolytic Adenovirus Expressing IL-23 and p35 Elicits IFN-gamma- and TNF-alpha-Co-Producing T Cell-Mediated Antitumor Immunityopen access
- Authors
- Choi, Il-Kyu; Li, Yan; Oh, Eonju; Kim, Jaesung; Yun, Chae-Ok
- Issue Date
- Jul-2013
- Publisher
- PUBLIC LIBRARY SCIENCE
- Citation
- PLOS ONE, v.8, no.7, pp.1 - 15
- Indexed
- SCIE
SCOPUS
- Journal Title
- PLOS ONE
- Volume
- 8
- Number
- 7
- Start Page
- 1
- End Page
- 15
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/26698
- DOI
- 10.1371/journal.pone.0067512
- ISSN
- 1932-6203
- Abstract
- Cytokine immunogene therapy is a promising strategy for cancer treatment. Interleukin (IL)-12 boosts potent antitumor immunity by inducing T helper 1 cell differentiation and stimulating cytotoxic T lymphocyte and natural killer cell cytotoxicity. IL-23 has been proposed to have similar but not overlapping functions with IL-12 in inducing Th1 cell differentiation and antitumor immunity. However, the therapeutic effects of intratumoral co-expression of IL-12 and IL-23 in a cancer model have yet to be investigated. Therefore, we investigated for the first time an effective cancer immunogene therapy of syngeneic tumors via intratumoral inoculation of oncolytic adenovirus co-expressing IL-23 and p35, RdB/IL23/p35. Intratumoral administration of RdB/IL23/p35 elicited strong antitumor effects and increased survival in a murine B16-F10 syngeneic tumor model. The levels of IL-12, IL-23, interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha) were elevated in RdB/IL23/p35-treated tumors. Moreover, the proportion of regulatory T cells was markedly decreased in mice treated with RdB/IL23/p35. Consistent with these data, mice injected with RdB/IL23/p35 showed massive infiltration of CD4(+) and CD8(+) T cells into the tumor as well as enhanced induction of tumor-specific immunity. Importantly, therapeutic mechanism of antitumor immunity mediated by RdB/IL23/p35 is associated with the generation and recruitment of IFN-gamma- and TNF-alpha-co-producing T cells in tumor microenvironment. These results provide a new insight into therapeutic mechanisms of IL-12 plus IL-23 and provide a potential clinical cancer immunotherapeutic agent for improved antitumor immunity.
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