Concurrent delivery of tumor antigens and activation signals to dendritic cells by irradiated CD40 ligand-transfected tumor cells resulted in efficient activation of specific CD8+ T cells
| Autor: | Shin-Hun Juang, Yi Mei Hung, Sheng Ru Shiou, Ko Jiunn Liu, Jacqueline Whang-Peng, Li-Fan Lu, Hui Ting Cheng |
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| Rok vydání: | 2003 |
| Předmět: |
Cancer Research
CD40 Ligand Immunoglobulins chemical and pharmacologic phenomena Biology Lymphocyte Activation Transfection Cancer Vaccines Mice Th2 Cells Antigen Antigens CD Antigens Neoplasm Cell Line Tumor Animals Humans Cytotoxic T cell Antigen-presenting cell Molecular Biology Membrane Glycoproteins CD40 Follicular dendritic cells hemic and immune systems Dendritic Cells Neoplasms Experimental Dendritic cell Th1 Cells Coculture Techniques Immunology biology.protein Cancer research Interleukin 12 Cytokines Molecular Medicine CD8 T-Lymphocytes Cytotoxic |
| Zdroj: | Cancer Gene Therapy. 11:135-147 |
| ISSN: | 1476-5500 0929-1903 |
| DOI: | 10.1038/sj.cgt.7700663 |
| Popis: | To improve the efficacy of tumor cell-based and dendritic cell (DC)-based cancer vaccines, this study explored the potential of a new cancer vaccine strategy, that is, the use of CD40 ligand-transfected tumor (CD40L-tumor) cells to simultaneously deliver both tumor-derived antigens (Ag) and maturation stimuli to DCs. Materials from frozen/thawed or irradiated human tumor cells, with or without surface CD40L, were internalized efficiently by immature DCs after coincubation. However, during the internalization process, only coculturing with irradiated CD40L-tumor cells resulted in concurrent, optimal DC maturation and production of proinflammatory chemokines and pro-Th1 cytokines, such as IL-6, IL-8, IL-12, IFN-gamma, and TNF-alpha. These activated DCs were the most potent cells to support the growth of CD8+, IFN-gamma-producing T cells, and to process tumor Ag for the generation of specific cytotoxic T cells in vitro. Animals vaccinated with irradiated CD40L-tumor cell-pulsed DCs were better protected against subsequent challenge of a weakly immunogenic tumor cell line than animals vaccinated with irradiated CD40L-tumor cells alone. Thus, our results strongly support the future clinical application of using DCs pulsed with irradiated CD40L-tumor cells as a cancer vaccine. |
| Databáze: | OpenAIRE |
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