Oncolytic adenovirus co-expressing IL-12 and IL-18 improves tumor-specific immunity via differentiation of T cells expressing IL-12Rβ2 or IL-18Rαopen access
- Authors
- Choi, I-K; Lee, J-S; Zhang, S-N; Park, J.; Lee, K-M; Sonn, C. H.; Yun, C-O
- Issue Date
- Sep-2011
- Publisher
- SPRINGERNATURE
- Keywords
- cancer immunogene therapy; oncolytic adenovirus; IL-12; IL-18; T cells expressing IL-12R beta 2 or IL-18R alpha
- Citation
- GENE THERAPY, v.18, no.9, pp.898 - 909
- Indexed
- SCIE
SCOPUS
- Journal Title
- GENE THERAPY
- Volume
- 18
- Number
- 9
- Start Page
- 898
- End Page
- 909
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/27710
- DOI
- 10.1038/gt.2011.37
- ISSN
- 0969-7128
- Abstract
- The oncolytic adenovirus (Ad) is currently being advanced as a promising antitumor remedy as it selectively replicates in tumor cells and can transfer and amplify therapeutic genes. Interleukin (IL)-12 induces a potent antitumor effect by promoting natural killer (NK) cell and cytotoxic T cell activities. IL-18 also augments cytotoxicity of NK cells and proliferation of T cells. This effect further enhances the function of IL-12 in a synergistic manner. Therefore, we investigated for the first time an effective cancer immunogene therapy of syngeneic tumors via intratumoral administration of oncolytic Ad co-expressing IL-12 and IL-18, RdB/IL-12/IL-18. Intratumoral administration of RdB/IL-12/IL-18 improved antitumor effects, as well as increased survival, in B16-F10 murine melanoma model. The ratio of T-helper type 1/2 cytokine as well as the levels of IL-12, IL-18, interferon-gamma and granulocyte-macrophage colony-stimulating factor was markedly elevated in RdB/IL-12/IL-18-treated tumors. Mice injected with RdB/IL-12/IL-18 also showed enhanced cytotoxicity of tumor-specific immune cells. Consistent with these results, immense necrosis and infiltration of NK cells, as well as CD4(+) and CD8(+) T cells, were observed in RdB/IL-12/IL-18-treated tumor tissues. Importantly, tumors treated with RdB/IL-12/IL-18 showed an elevated number of T cells expressing IL-12R beta 2 or IL-18R alpha. These results provide a new insight into therapeutic mechanisms of IL-12 plus IL-18 and provide a potential clinical cancer immunotherapeutic agent for improved antitumor immunity.
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