Dendritic cell therapy with interferon-α synergistically suppresses outgrowth of established tumors in a murine colorectal cancer model

Ishii, Shigeaki; Hiroishi, Kazumasa; Eguchi, Junichi; Hiraide, Ayako; Imawari, Michio

doi:10.1038/sj.gt.3302608

Cited by 12 publications

(20 citation statements)

References 30 publications

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“…The effect of IFN I cancer treatment is likely attributable to a number of mechanisms. For example, IFN I can assist in maintaining T cell viability in the tumor microenvironment, reinforce NK activation, and activate endogenous DCs for tumor antigen cross-presentation (37)(38)(39)(40). IFN I may also alter the tumor directly, for example, by inducing upregulation of MHC I molecules on tumor cells (38,41).…”

Section: Discussionmentioning

confidence: 99%

IL-15 and Type I Interferon Are Required for Activation of Tumoricidal NK Cells by Virus-Infected Dendritic Cells

et al. 2011

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There is increasing evidence that natural killer (NK) cells play an important role in antitumor immunity following dendritic cell (DC) vaccination. Little is known, however, about the optimal stimulation of DCs that favors NK activation in tumor-bearing hosts. In this study, we demonstrate that treatment with toll-like receptor (TLR) ligands and infection with a mutant vesicular stomatitis virus (VSV-DM51) both induced DC maturation. Further, inoculation of these DCs led to robust NK-mediated protection against tumor challenge. Strikingly, only VSV-DM51-infected DCs were capable of suppressing the growth of established tumors, suggesting that additional signals provided by viral infection may be required to activate tumoricidal NK cells in tumorbearing hosts. VSV-DM51 infection of DCs induced greater type I interferon (IFN I) production than TLR ligand treatment, and disruption of the IFN I pathway in DCs eliminated their ability to induce NK activation and tumor protection. However, further studies indicated that IFN I alone was not sufficient to activate NK cells, especially in the presence of a tumor, and DC-derived IL-15 was additionally required for tumoricidal NK activation. These results suggest that induction of IFN I by VSV-DM51 allows DCs to overcome tumor-associated immunosuppression and facilitate IL-15-mediated priming of tumoricidal NK cells. Thus, the mode of DC maturation should be carefully considered when designing DC-based cancer immunotherapies. Cancer Res; 71(7); 2497-506. Ó2011 AACR.

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Section: Discussionmentioning

confidence: 99%

IL-15 and Type I Interferon Are Required for Activation of Tumoricidal NK Cells by Virus-Infected Dendritic Cells

et al. 2011

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“…Dendritic cells were generated from bone marrow cells of B6 mice using murine granulocyte-macrophage colony-stimulating factor (10 ng ml --1 ) and IL-4 (10 ng ml --1 ) that was obtained from PeproTech EC (London, England), as reported previously. 36 Cytolytic assays were performed 7 days after the last stimulation using the responder cells as effector cells. 3 ) and various numbers of effector cells at the indicated effector to target ratios (E:T) were plated in 200 ml of complete medium in each well of the 96-well round-bottom plates.…”

Section: In Vivo Antibody-mediated Depletion Of Leukocytesmentioning

confidence: 99%

Effects of interferon-α-transduced tumor cell vaccines and blockade of programmed cell death-1 on the growth of established tumors

et al. 2012

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“…, KUN A30P VLP-infected cells produced about 6 ng IFN-a/b/10 6 cells every 18 h, which is comparable to the 7.8 ng IFN-a/10 6 cells every 18 h produced by tumour cells transfected with a DNA plasmid encoding IFN-a, 43 but at an order of magnitude less than that produced by tumour cells transfected with an adenovirus vector encoding IFN-a. 35 All experiments described herein used KUN GM-CSF VLPs containing the NS2A/A30P mutation.…”

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confidence: 68%

A Kunjin replicon vector encoding granulocyte macrophage colony-stimulating factor for intra-tumoral gene therapy

et al. 2008

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We have recently developed a non-cytopathic RNA repliconbased viral vector system based on the flavivirus Kunjin. Here, we illustrate the utility of the Kunjin replicon system for gene therapy. Intra-tumoral injections of Kunjin replicon virus-like particles encoding granulocyte colony-stimulating factor were able to cure 450% of established subcutaneous CT26 colon carcinoma and B16-OVA melanomas. Regression of CT26 tumours correlated with the induction of anticancer CD8 T cells, and treatment of subcutaneous CT26 tumours also resulted in the regression of CT26 lung metastases. Only a few immune-based strategies are able to cure these aggressive tumours once they are of a reasonable size, illustrating the potential of this vector system for intra-tumoral gene therapy applications.

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Dendritic cell therapy with interferon-α synergistically suppresses outgrowth of established tumors in a murine colorectal cancer model

Cited by 12 publications

References 30 publications

IL-15 and Type I Interferon Are Required for Activation of Tumoricidal NK Cells by Virus-Infected Dendritic Cells

IL-15 and Type I Interferon Are Required for Activation of Tumoricidal NK Cells by Virus-Infected Dendritic Cells

Effects of interferon-α-transduced tumor cell vaccines and blockade of programmed cell death-1 on the growth of established tumors

A Kunjin replicon vector encoding granulocyte macrophage colony-stimulating factor for intra-tumoral gene therapy

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