gms | German Medical Science

27th German Cancer Congress Berlin 2006

German Cancer Society (Frankfurt/M.)

22. - 26.03.2006, Berlin

Article

Send article

Development of a Clinical-Grade Protocol to mature moncyte-derived dendritic cells in TH1-direction

Meeting Abstract

Search Medline for

  • corresponding author presenting/speaker Bernd Hildenbrand - Klinik für Tumorbiologie, Freiburg, Deutschland
  • Barbara Sauer - Klinik für Tumorbiologie, Freiburg
  • Marina Freudenberg - Max-Planck-Institut für Immunbiologie, Freiburg
  • Chris Galanos - Max-Planck-Institut für Immunbiologie, Freiburg
  • Christoph Kalis - Max-Planck-Institut für Immunbiologie, Freiburg
  • Gabi Niedermann - Radiologische Universitätsklinik, Freiburg
  • Christoph Stoll - Klinik für Tumorbiologie, Freiburg
  • Clemens Unger - Klinik für Tumorbiologie, Freiburg
  • Marc Azemar - Klinik für Tumorbiologie, Freiburg

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocPO631

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dkk2006/06dkk739.shtml

Published: March 20, 2006

© 2006 Hildenbrand et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

Text

Purpose: Dendritic cells (DC) can initiate primary adaptive immune responses and skew T cell reactivity toward a TH1 or TH2 pattern. We improved the capacity of clinical-grade monocyte-derived dendritic cells to elaborate IL-12 with special regard of their state of maturation, different maturation stimuli and its regulation by TH1/TH2-influencing cytokines.

Methods: Monocyte-derived DC were generated in serum-free medium with GM-CSF and IL-4 for 7 days and matured for another 24 or 48 h with PGE2, TNF-α, ± IL-6 , ± IL-1 and ± Interferon-γ. Matured DC were phenotypically characterised and measured for IL-6, IL-10 and IL-12 p70 by ELISA.

Results: All investigated clinical-grade protocols for maturation of monocyte-derived DC appeared able to provide the phenotypic characteristics necessary to initiate DC maturation. DC matured with PGE2 and TNF-α only resulted in high levels of IL-10 but only low levels of IL-12 p70. Addition of IL-1 and IL-6 (Jonuleit cocktail) and Interferon-γ lead to significant higher levels of bioactive IL-12 concomitant with lower levels of IL-10. Besides addition of INF-γ resulted in more pronounced upregulation of CD83, major histocompatibility complex class I and B7 molecules by DC

Conclusion: PGE2, TNF-α, IL-1, Il-6 and IFN-γ represent a suitable cytokine cocktail for the ex vivo maturation of monocyte-derived DC that can be used as cellular vaccines to promote a potent type 1 immune response.

Key Words: Dendritic cells, Maturation, Adjuvants, Cytokines, Immunotherapy