Administration route-dependent vaccine efficiency of murine dendritic cells pulsed with antigens

Okada, Naoki; Tsujino, M; Hagiwara, Yukari; Tada, Atsuko; Tamura, Yuki; Mori, Kohei; Saito, Tomomi; Nakagawa, Shinsaku; Mayumi, Tadanori; Fujita, Takuya; Yamamoto, Akira

doi:10.1054/bjoc.2001.1801

Cited by 69 publications

(56 citation statements)

References 41 publications

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“…50,51 Thus, for our DC-directed immunization approach, it was necessary to perform a broad study comparing the response generated by different vaccination routes. Naive B6 mice were immunized with the targeting lentivector FUW-hgp100/SVGmu (transduction units (TU) ¼ 5 Â 10 6 ) by s.c., f.p.…”

Section: Characterization Of Immune Responses Induced By Targeting Lementioning

confidence: 99%

Dendritic cell-directed lentivector vaccine induces antigen-specific immune responses against murine melanoma

Yang

Liang

et al. 2011

Cancer Gene Ther

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Lentivectors are potential vaccine delivery vehicles because they can efficiently transduce a variety of non-dividing cells, including antigen-presenting cells, and do not cause expression of extra viral proteins. To improve safety while retaining efficiency, a dendritic cell (DC)-specific lentivector was constructed by pseudotyping the vector with an engineered viral glycoprotein derived from Sindbis virus. We assessed the level of anti-tumor immunity conferred by this engineered lentivector encoding the melanoma antigen gp100 in a mouse model. Footpad injection of the engineered lentivectors results in the best antigen-specific immune response as compared with subcutaneous and intraperitoneal injections. A single prime vaccination of the engineered lentivectors can elicit a high frequency (up to 10%) of gp100-specific CD8 þ T cells in peripheral blood 3 weeks after the vaccination and this response will be maintained at around 5% for up to 8 weeks. We found that these engineered lentivectors elicited relatively low levels of anti-vector neutralizing antibody responses. Importantly, direct injection of this engineered lentivector inhibited the growth of aggressive B16 murine melanoma. These data suggest that DC-specific lentivectors can be a novel and alternative vaccine carrier with the potential to deliver effective anti-tumor immunity for cancer immunotherapy.

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Section: Characterization Of Immune Responses Induced By Targeting Lementioning

confidence: 99%

Dendritic cell-directed lentivector vaccine induces antigen-specific immune responses against murine melanoma

Yang

Liang

et al. 2011

Cancer Gene Ther

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“…Target cells (IFN-gstimulated or untreated B16BL6, EL4 cells, and YAC-1 cells) were Eu-labeled and an Eu-release assay was performed as previously described. 55 Cytolytic activity was determined using the following formula: (% of lysis)¼((experimental Eu-releaseÀspontaneous Eu-release)/(maximum EureleaseÀspontaneous Eu-release)) Â 100. Spontaneous Eurelease of the target cells was o10% of maximum Eu-release by detergent in all assays.…”

Section: Eu-release Assay For Cytolytic Activity Of Nk Cells and Ctlsmentioning

confidence: 99%

Dendritic cells transduced with gp100 gene by RGD fiber-mutant adenovirus vectors are highly efficacious in generating anti-B16BL6 melanoma immunity in mice

et al. 2003

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Dendritic cells (DCs) are the most potent professional antigen-presenting cells for the initiation of antigen-specific immune responses, and antigen-loaded DCs have been regarded as promising vaccines in cancer immunotherapy. We previously demonstrated that RGD fiber-mutant adenovirus vector (AdRGD) could attain highly efficient gene transduction into human and murine DCs. The aim of the present study is to demonstrate the predominance of ex vivo genetic DC manipulation using AdRGD in improving the efficacy of DC-based immunotherapy targeting gp100, a melanoma-associated antigen (MAA). Vaccination with murine bone marrow-derived DCs transduced with AdRGD encoding gp100 (AdRGD-gp100/mBM-DCs) dramatically improved resistance to B16BL6 melanoma challenge and pulmonary metastasis as compared with immunization with conventional Ad-gp100-transduced mBM-DCs. The improvement in antimelanoma effects upon immunization with AdRGD-gp100/mBM-DCs correlated with enhanced cytotoxic activities of natural killer (NK) cells and B16BL6-specific cytotoxic T lymphocytes (CTLs). Furthermore, in vivo depletion analysis demonstrated that CD8 þ CTLs and NK cells were the predominant effector cells responsible for the anti-B16BL6 immunity induced by vaccination with AdRGDgp100/mBM-DCs, and that helper function of CD4 þ T cells was necessary for sufficiently eliciting effector activity. These findings clearly revealed that highly efficient MAA gene transduction to DCs by AdRGD could greatly improve the efficacy of DC-based immunotherapy against melanoma.

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“…Target cells (IFN-g-stimulated B16BL6, IFN-g-stimulated EL4, and YAC-1 cell) were europium-labeled and a europiumrelease assay was performed as previously described. 32 Cytolytic activity was determined using the following formula: (% of lysis) ¼ ((experimental europium-releaseÀspontaneous europium-release)/(maximum europiumreleaseÀspontaneous europium-release)) Â 100. Spontaneous europium-release of the target cells was o15% of maximum europium-release by detergent.…”

Section: Histopathological and Immunohistochemical Examination Of Tummentioning

confidence: 99%

Tumor suppressive efficacy through augmentation of tumor-infiltrating immune cells by intratumoral injection of chemokine-expressing adenoviral vector

et al. 2005

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Our goal in the present study was to evaluate antitumor effects and frequency of tumor-infiltrating immune cells upon intratumoral injection of RGD fiber-mutant adenoviral vector (AdRGD) encoding the chemokines CCL17, CCL19, CCL20, CCL21, CCL22, CCL27, XCL1, and CX3CL1. Among eight kinds of chemokine-expressing AdRGDs, AdRGD-CCL19 injection most efficiently induced infiltration of T cells into established B16BL6 tumor parenchyma, whereas most of these T cells were perforin-negative in immunohistochemical analysis. Additionally, the growth of AdRGD-CCL19-injected tumors decreased only slightly as well as that of other tumors treated with each chemokine-expressing AdRGD, which indicated that accumulation of naive T cells in tumor tissue does not effectively damage the tumor cells. Tumor-bearing mice, in which B16BL6-specific T cells were elicited by dendritic cellbased immunization, demonstrated that intratumoral injection of AdRGD-CCL17, -CCL22, or -CCL27 could considerably suppress tumor growth and attract activated T cells. On the other hand, AdRGD-CCL19-injection in the immunized mice showed slight increase of tumor-infiltrating T cells compared to treatment using control vector. Collectively, although AdRGD-mediated chemokine gene transduction into established tumors would be very useful for augmentation of tumor-infiltrating immune cells, a combinational treatment that can systemically induce tumor-specific effector T cells is necessary for satisfactory antitumor efficacy.

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Administration route-dependent vaccine efficiency of murine dendritic cells pulsed with antigens

Cited by 69 publications

References 41 publications

Dendritic cell-directed lentivector vaccine induces antigen-specific immune responses against murine melanoma

Dendritic cell-directed lentivector vaccine induces antigen-specific immune responses against murine melanoma

Dendritic cells transduced with gp100 gene by RGD fiber-mutant adenovirus vectors are highly efficacious in generating anti-B16BL6 melanoma immunity in mice

Tumor suppressive efficacy through augmentation of tumor-infiltrating immune cells by intratumoral injection of chemokine-expressing adenoviral vector

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