Murine dendritic cells transfected with human GP100 elicit both antigen-specific CD8+ and CD4+ T-cell responses and are more effective than DNA vaccines at generating anti-tumor immunity

Yang, Shan; Vervaert, Carol E.; Burch, James A.; Grichnik, James M.; Seigler, Hilliard F.; Darrow, Timothy L.

doi:10.1002/(sici)1097-0215(19991112)83:4<532::aid-ijc16>3.0.co;2-k

Cited by 53 publications

(32 citation statements)

References 18 publications

(3 reference statements)

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“…Lastly, DC can express tumor antigens continuously and MHC-peptide complexes for long periods. 6,10 Nevertheless, the antitumor immunity induced by TAA gene-modified DC vaccine is still limited in clinical trials, 11,12 suggesting that DC-based vaccine will need to be modified to improve the efficacy before being widely used. So, the primary aim of our present study is to enhance the therapeutic efficacy of DC-based vaccine by genetic modification of DC.…”

Section: Ance To Tumor Challenge Most Effectively It Was Found That mentioning

confidence: 99%

“…with DC transferred with TAA gene offers the advantage of presenting multiple epitopes in the context of MHC class I and class II molecules, 6 and it seems to be an attractive approach for cancer immunotherapy. Different viral vectors, including retroviral vector, 26 Ad vector, 27 and vaccinia vector, 28,29 have been evaluated to genetically modify DC.…”

Section: Figure 8 Suppression Of the Tumor Growth And Extension Of Thmentioning

confidence: 99%

“…Based on these features and development of the methods for expansion of DC on a large scale from hematopoietic precursors, 5 DC have attracted great attention as the vehicles for the delivery of cancer vaccines. 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%

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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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Section: Ance To Tumor Challenge Most Effectively It Was Found That mentioning

confidence: 99%

Section: Figure 8 Suppression Of the Tumor Growth And Extension Of Thmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2002

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“…Furthermore, TAA gene-modified DCs may also present MHC class IIrestricted epitope(s) to CD4 þ T cells, and can express TAA continuously and MHC-peptide complexes for long periods. [7][8][9] Among various techniques for transferring the TAA gene to DCs, the ex vivo engineering of DCs using adenovirus vector (Ad) provides encouraging results. [10][11][12] However, the low or lack of coxsackie-adenovirus receptor (primary Ad-receptor) expression on the DC surface makes sufficient gene transduction to DCs by conventional Ad difficult.…”

Section: Introductionmentioning

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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“…3 However, in this model, genetically modified DC generated antigen-specific CTL independent of NK cells. Multiple additional murine models confirmed that tumor antigen gene-modified DC directly stimulate CD8 þ CTL, usually requiring CD4 T help, [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] which was shown to be mediated by CD40 crosslinking of the DC. 27 Two reports have shown that NK1.1 þ cells may be involved in the antitumor response generated by tumor antigen gene-modified DC.…”

mentioning

confidence: 99%

Natural killer cells play a critical role in the immune response following immunization with melanoma-antigen-engineered dendritic cells

et al. 2005

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Tumor antigen gene-modified dendritic cells (DC) generates robust antigen-specific protective antitumor responses. Though the role of CD4 positive and CD8 positive cells in the immunological response to gene-modified DC has been well-characterized, the role of NK cells in this response has been somewhat less clear. Owing to the significant contribution of innate immunity in other model systems, we postulated that NK cells would hold a critical position in the generation of an immune response following immunization with tumor antigen-engineered DC. Immunization with MART-1 melanoma antigen-engineered DC in C57BL/6 mice resulted in the generation of antigen-specific cytotoxic T lymphocytes and in vivo protective responses to the murine B16 melanoma. These responses were dependent on the presence of functional NK cells, although NK cells alone were not sufficient in generating protective responses. Adoptive transfer of NK cells into an NK-deficient but T-cell-competent environment restored the protective response to gene-modified DC immunization. In conclusion, protective immunity after tumor antigen gene-modified DC immunization requires collaboration between CD4 þ and CD8 þ T cells and NK cells.

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Murine dendritic cells transfected with human GP100 elicit both antigen-specific CD8+ and CD4+ T-cell responses and are more effective than DNA vaccines at generating anti-tumor immunity

Cited by 53 publications

References 18 publications

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

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

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

Natural killer cells play a critical role in the immune response following immunization with melanoma-antigen-engineered dendritic cells

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