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Enhanced tumor-specific immunity of oncolytic adenovirus co-expressing IL-12 and IL-23

Issue Date
2012
Description
Graduate Program for Nanomedical Science/박사
Abstract
Cytokine immunogene therapy is a promising strategy for cancer treatment. Interleukin (IL)-12 boosts potent antitumor immunity by inducing T helper 1 (Th1) cell differentiation and stimulating cytotoxic T lymphocyte (CTL) and natural killer (NK) 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 (Ad) 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-γ (IFN-γ), and tumor necrosis factor-(TNF-) 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 immune mediated by RdB/IL23/p35 is associated with the generation and recruitment of IFN-γ- and TNF--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.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/133887
Appears in Collections:
2. 학위논문 > 5. Others > 기타 학위논문
Yonsei Authors
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