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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

Cancer Gene Therapy volume 11, pages 135–147 (2004)Cite this article

Abstract

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-γ, and TNF-α. These activated DCs were the most potent cells to support the growth of CD8+, IFN-γ-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.

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Acknowledgements

We would like to thank a former collaborator, Dr Kun-Tai Lu, at the National Taiwan University Hospital, for providing malignant pleural effusions and a former senior technician, Mrs Den-Mei Yang, for her technical assistance in establishing the human lung cancer cell line.

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Authors and Affiliations

  1. Division of Cancer Research, Cancer Research Cooperative Laboratory at National Taiwan University Hospital, National Health Research Institutes, Taipei, Taiwan

    Ko-Jiunn Liu, Li-Fan Lu, Hui-Ting Cheng, Yi-Mei Hung, Sheng-Ru Shiou, Jacqueline Whang-Peng & Shin-Hun Juang

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Correspondence to Ko-Jiunn Liu.

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This work was supported by intramural grants from the National Health Research Institutes, Taipei, Taiwan.

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Liu, KJ., Lu, LF., Cheng, HT. et al. 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. Cancer Gene Ther 11, 135–147 (2004). https://doi.org/10.1038/sj.cgt.7700663

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