Adenovirus-mediated gene transfer of interleukin-23 shows prophylactic but not therapeutic antitumor effects

Ht, Jin; Youn, Ji Youn; Sy, Choi; Sh, Seo; Park, Sang Hoon; My, Song; Sh, Yang; Sung, YC

doi:10.1038/cgt.2008.41

Cited by 8 publications

(5 citation statements)

References 50 publications

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“…It is also necessary to note that while this manuscript was in preparation, a paper demonstrating a prophylactic, but not therapeutic, effect of adenovirally delivered IL-23 in variety of murine tumors was published25. This disparity in results may be due to the use of different murine tumor models, use of a mutant form of p4025 or initiating treatment at a different stage of the tumor model.…”

Section: Discussionmentioning

confidence: 99%

“…This disparity in results may be due to the use of different murine tumor models, use of a mutant form of p4025 or initiating treatment at a different stage of the tumor model. In our studies, tumor bearing mice were treated on days 7, 9 and 11 starting with an average tumor size of 4mm compared to the studies performed in the previously mentioned paper, in which treatment was initiated when the average tumor volume reached 7mm in diameter.…”

Section: Discussionmentioning

confidence: 99%

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Adenoviral-mediated, intratumor gene transfer of interleukin 23 induces a therapeutic antitumor response

et al. 2009

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IL-23 is a member of the IL-12 family of heterodimeric cytokines, comprised of p19 and p40 subunits, which exhibits immunostimulatory properties similar to IL-12. IL-23 has been shown to possess potent anti-tumor activities in several establishment models of cancer and a few therapeutic models, but the efficacy of local, adenoviral-mediated expression of IL-23 in established tumors has yet to be investigated. Here we have examined the anti-tumor activity of adenovirally-delivered IL-23 in a day 7 MCA205 murine fibrosarcoma tumor model. Three intratumoral injections of adenovirus expressing IL-23 (Ad.IL-23) significantly increased animal survival and resulted in complete rejection of 40 percent of tumors, with subsequent generation of protective immunity and MCA205-specific cytotoxic T-lymphocytes (CTLs). Additionally, we have shown that the anti-tumor activity of IL-23 is independent of IL-17, perforin and Fas ligand, but dependent on IFN-γ, CD4 and CD8 positive T-cells. These results demonstrate that direct intratumoral injection of adenovirus expressing IL-23 results in enhanced survival, tumor eradication and generation of protective immunity by generation of a Th1-type immune response.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Adenoviral-mediated, intratumor gene transfer of interleukin 23 induces a therapeutic antitumor response

et al. 2009

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“…The ELISPOT assay was performed as described before [35]. Briefly, splenocytes were co-incubated with E7 CD8 peptide (49-57) on an IFN-g capture Ab (BD Bioscience)-coated 96-well ELISPOT plate (Millipore).…”

Section: Elispot Assaymentioning

confidence: 99%

Marked enhancement of antigen‐specific T‐cell responses by IL‐7‐fused nonlytic, but not lytic, Fc as a genetic adjuvant

et al. 2010

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IL-7 plays a crucial role in the homeostatic proliferation, differentiation and survival of T cells, as well as in the survival and proliferation of precursor B cells. Here, we demonstrated that utilizing nonlytic Fc-fused IL-7 (IL-7-Fc m ) as a genetic adjuvant significantly enhanced not only CD4 1 but also CD8 1 T-cell responses by E7 DNA immunization, in addition to improving protection against TC-1-induced tumors in comparison to IL-7 alone. Similar results were obtained in OT-1 adoptive transfer experiments with OVA DNA injection, suggesting independence from antigenic nature and experimental conditions. In particular, the increased frequency of CD8 1 T cells was mainly due to enhanced T-cell proliferation in T-cell priming, and not to decreased cellular apoptosis. Interestingly, the enhanced adjuvant effect was not seen in the co-delivery of lytic Fc-fused IL-7 (IL-7-Fc) which increases T-cell apoptosis as well as T-cell proliferation, suggesting that the T-cell proliferative effect may be neutralized by T-cell apoptosis. Thus, our findings suggest that nonlytic Fc, in contrast to lytic Fc, fusion to cytokines may provide an insight in designing a potent genetic adjuvant for inducing CD4 1 and CD8 1 T-cell responses.

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“…For example, mouse tumor cell lines expressing IL-23 can inhibit tumor growth in vivo (31); the use of adenovirus expressing IL-23 in established tumor models exhibited antitumor effects (32). It has also been reported that IL-23 can significantly enhance its antitumor effect only after adoptive transfer of peptide vaccine or antigen-specific T cells (33). The drawback of the aforementioned in vivo experiment is that it cannot accurately explain whether IL-23 acts directly on tumor cells and how to regulate its biological processes.…”

Section: Discussionmentioning

confidence: 99%

IL‑23 concentration‑dependently regulates T24 cell proliferation, migration and invasion and is associated with prognosis in patients with bladder cancer

Wang

Zhang

et al. 2018

Oncol Rep

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Interleukin-23 (IL-23, also known as IL23A), is an important proinflammatory cytokine whose role in the development and progression of tumors remains controversial. The present study on IL-23 focused on its impact on the tumor microenvironment. Existing studies on its direct role on tumor cells are limited. Previously, we reported that the expression level of IL-23 in human bladder urothelial carcinoma was significantly higher than that in adjacent tissues as determined by immunohistochemistry. In this study, we further validated the results of immunohistochemistry using the Oncomine database and we found that IL23A expression in non-muscle invasive bladder urothelial carcinoma (NMIBC) was significantly higher than that in muscle invasive bladder urothelial carcinoma (MIBC). Expression of IL23A was negatively correlated with the clinical stage of bladder urothelial carcinoma and had a positive correlation with prognosis. In vitro experiments revealed that different concentrations of IL-23 had different effects on T24 cells. A low concentration of 20 ng/ml IL-23 promoted T24 cell proliferation, migration, invasion and EMT transformation, while a high concentration of 40 ng/ml IL-23 inhibited these functions. These results indicated that IL-23 plays a dual role in the progression of bladder cancer. Low concentrations of IL-23 promote bladder tumor progression, while high concentrations of IL-23 have the opposite effect.

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Adenovirus-mediated gene transfer of interleukin-23 shows prophylactic but not therapeutic antitumor effects

Cited by 8 publications

References 50 publications

Adenoviral-mediated, intratumor gene transfer of interleukin 23 induces a therapeutic antitumor response

Adenoviral-mediated, intratumor gene transfer of interleukin 23 induces a therapeutic antitumor response

Marked enhancement of antigen‐specific T‐cell responses by IL‐7‐fused nonlytic, but not lytic, Fc as a genetic adjuvant

IL‑23 concentration‑dependently regulates T24 cell proliferation, migration and invasion and is associated with prognosis in patients with bladder cancer

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