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- Title
Enhanced antimetastatic effect of fetal liver kinase 1 extracellular domain and interferon-gamma fusion gene-modified dendritic cell vaccination.
- Authors
Pan, J.; Heiser, A.; Marget, M.; Steinmann, J.; Kabelitz, D.
- Abstract
Antiangiogenic immunotherapy benefits from targeting antigens expressed on genetically stable endothelial cells and represents a novel modality for cancer treatment. Vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2, also known as flk1 in mouse) mediated VEGF signaling is the key rate-limiting step in angiogenesis. Blockade of the flk1 signaling pathway can significantly inhibit tumor cell-induced angiogenesis and lead to inhibition of tumor metastasis. Interferon-gamma (IFN-?) is a pleiotropic cytokine, which plays an important role in cell-mediated immunity. In this study, we tested the hypothesis that immunization of mice with soluble flk1 (sflk1) and IFN-?fusion gene-transfected dendritic cells (DC-sflk1-IFN-?) would induce a potent CTL response to flk1, leading to an inhibition of tumor-induced angiogenesis and metastasis. Our data show that immunization of mice with sflk1 gene-modified DC (DC-sflk1) could induce a CTL response to flk1, leading to profound inhibition of tumor-cell-induced angiogenesis and metastasis. However, more striking antimetastatic effects were achieved through induction of enhanced CTL response to flk1 and augmented inhibition of angiogenesis when mice were immunized with DC-sflk1-IFN-?. In vivo T-cell subset depletion experiments showed that CD8+ T cells were mainly responsible for this antimetastatic effect. Our data extend the notion that DC-based active antiangiogenic immunotherapy is an effective modality for cancer treatment, and show that the antitumor efficacy of this strategy can be improved by combination with DC-based cytokine immunotherapy.Gene Therapy (2005) 12, 742-750. doi:10.1038/sj.gt.3302470 Published online 24 February 2005
- Subjects
CANCER immunotherapy; CELL receptors; VASCULAR endothelial growth factors; TUMOR growth; ANTINEOPLASTIC agents; ANIMAL models of cancer
- Publication
Gene Therapy, 2005, Vol 12, Issue 9, p742
- ISSN
0969-7128
- Publication type
Article
- DOI
10.1038/sj.gt.3302470