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.
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.
Liu
Ko-Jiunn
KJ
Cancer Research Cooperative Laboratory at National Taiwan University Hospital, Division of Cancer Research, National Health Research Institutes, Taipei, Taiwan. kojiunn@nhri.org.tw
Lu
Li-Fan
LF
Cheng
Hui-Ting
HT
Hung
Yi-Mei
YM
Shiou
Sheng-Ru
SR
Whang-Peng
Jacqueline
J
Juang
Shin-Hun
SH
D000818:Animals; D015703:Antigens, CD; D000951:Antigens, Neoplasm / Q000276:immunology*; D023201:CD40 Ligand / Q000235:genetics* / Q000378:metabolism; D019496:Cancer Vaccines; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D009374:Neoplasms, Experimental / Q000276:immunology / Q000517:prevention & control*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014162:Transfection; D000097802:CD83 Antigen
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D023201:CD40 Ligand; D019496:Cancer Vaccines; D016207:Cytokines; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen