TY - JOUR
T1 - 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
AU - Liu, Ko Jiunn
AU - Lu, Li Fan
AU - Cheng, Hui Ting
AU - Hung, Yi Mei
AU - Shiou, Sheng Ru
AU - Whang-Peng, Jacqueline
AU - Juang, Shin Hun
N1 - Funding Information:
Address correspondence and reprint requests to: Dr Ko-Jiunn Liu, Cancer Research Cooperative Laboratory at National Taiwan University Hospital, Division of Cancer Research, National Health Research Institutes, 7, Chung-Shan South Road, 100 Taipei, Taiwan. E-mail: [email protected] This work was supported by intramural grants from the National Health Research Institutes, Taipei, Taiwan.
PY - 2004/2/1
Y1 - 2004/2/1
N2 - 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.
AB - 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.
KW - Antigen processing
KW - CD40 ligand
KW - Dendritic cells
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U2 - 10.1038/sj.cgt.7700663
DO - 10.1038/sj.cgt.7700663
M3 - Article
C2 - 14647233
AN - SCOPUS:0942268831
SN - 0929-1903
VL - 11
SP - 135
EP - 147
JO - Cancer Gene Therapy
JF - Cancer Gene Therapy
IS - 2
ER -