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

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

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)135-147
Number of pages13
JournalCancer Gene Therapy
Volume11
Issue number2
DOIs
Publication statusPublished - Feb 1 2004
Externally publishedYes

Keywords

  • Antigen processing
  • CD40 ligand
  • Dendritic cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

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