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CD40 activation in vivo overcomes peptide-induced peripheral cytotoxic T-lymphocyte tolerance and augments anti-tumor vaccine efficacy

Nature Medicine, ISSN: 1078-8956, Vol: 5, Issue: 7, Page: 774-779
1999
  • 433
    Citations
  • 0
    Usage
  • 130
    Captures
  • 0
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    433
    • Citation Indexes
      425
    • Patent Family Citations
      7
      • Patent Families
        7
    • Policy Citations
      1
      • Policy Citation
        1
  • Captures
    130

Article Description

The outcome of antigen recognition by naive CD8 cytotoxic T lymphocytes (CTLs) in the periphery is orchestrated by CD4 T-helper cells, and can either lead to priming or tolerization. The presence of T-helper cells favors the induction of CTL immunity, whereas the absence of T-helper cells can result in CTL tolerance. The action of T helper cells in CTL priming is mediated by CD40-CD40 ligand interactions. We demonstrate here that triggering of CD40 in vivo can considerably enhance the efficacy of peptide-based anti-tumor vaccines. The combination of a tolerogenic peptide vaccine containing a minimal essential CTL epitope with an activating antibody against CD40 converts tolerization into strong CTL priming. Moreover, CD40 ligation can provide an already protective tumor-specific peptide vaccine with the capacity to induce therapeutic CTL immunity in tumor-bearing mice. These findings indicate that the CD40-CD40 ligand pair can act as a 'switch', determining whether naive peripheral CTLs are primed or tolerized, and support the clinical use of CD40-stimulating agents as components of anti-cancer vaccines.

Bibliographic Details

Linda Diehl; Annemieke Th. den Boer; Stephen P. Schoenberger; Ellen I.H. van der Voort; Ton N.M. Schumacher; Cornelis J.M. Melief; Rienk Offringa; Rene E. M. Toes

Springer Science and Business Media LLC

Biochemistry, Genetics and Molecular Biology

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