Gene-based cancer vaccines: an ex vivo approach

Tendeloo, V. F. I. Van; Broeckhoven, Christine Van; Berneman, Zwi

doi:10.1038/sj.leu.2402069

Cited by 31 publications

(18 citation statements)

References 176 publications

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“…[10][11][12] Nevertheless, the antitumor immunity induced by TAA gene-modified DC vaccine is still limited in clinical trials, 38,39 suggesting that the breakthrough capable of improving the efficacy of DC-based immunotherapy will need to be explored for wide application of this novel cancer treatment. The antitumor efficacy of immunization with DCs genetically modified with TAA gene is still far from satisfactory in translational research and early phase clinical trials for a variety of reasons and is partly due to the relative resistance of DCs against gene transduction.…”

Section: Antimelanoma Effect Of Dcs Transduced By Adrgd-gp100mentioning

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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Section: Antimelanoma Effect Of Dcs Transduced By Adrgd-gp100mentioning

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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“…In the interest of space, we focus our attention on therapies targeting monogenic disorders. For a good review that relates the danger model to gene-based strategies for cancer therapy, refer to Van Tendeloo et al 5 …”

Section: Introductionmentioning

confidence: 99%

Dangerous liaisons: the role of “danger” signals in the immune response to gene therapy

Brown

Lillicrap

2002

Blood

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“…Genetic modification of DC to express tumor-associated antigen (TAA) has been documented to be efficacious to induce antitumor immunity in many animal models 6,7 and partial clinical trials. 8,9 Transfection of DC with an entire TAA gene has…”

Section: Introductionmentioning

confidence: 99%

Lymphotactin cotransfection enhances the therapeutic efficacy of dendritic cells genetically modified with melanoma antigen gp100

et al. 2002

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Lymphotactin (Lptn) is a C chemokine that attracts T cells and NK cells. Dendritic cells (DC) are highly efficient, specialized antigen-presenting cells and antigen-pulsed DC has been regarded as promising vaccines in cancer immunotherapy. The aim of our present study is to improve the therapeutic efficacy of DC-based tumor vaccine by increasing the preferential chemotaxis of DC to T cells. In this study, Lptnand/or melanoma-associated antigen gp100 were transfected into mouse bone marrow-derived DC, which were used as vaccines in B16 melanoma model.

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Gene-based cancer vaccines: an ex vivo approach

Cited by 31 publications

References 176 publications

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

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

Dangerous liaisons: the role of “danger” signals in the immune response to gene therapy

Lymphotactin cotransfection enhances the therapeutic efficacy of dendritic cells genetically modified with melanoma antigen gp100

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