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Combined dendritic cell- and CpG oligonucleotide-based immune therapy cures large murine tumors that resist chemotherapy.

Authors
  • Heckelsmiller, Klaus
  • Beck, Sebastian
  • Rall, Katharina
  • Sipos, Bence
  • Schlamp, Angelika
  • Tuma, Evelyn
  • Rothenfusser, Simon
  • Endres, Stefan
  • Hartmann, Gunther
Type
Published Article
Journal
European journal of immunology
Publication Date
Nov 01, 2002
Volume
32
Issue
11
Pages
3235–3245
Identifiers
PMID: 12555669
Source
Medline
License
Unknown

Abstract

The use of dendritic cells (DC) loaded with tumor antigen is one of the most advanced approaches in cancer immunotherapy. CpG motifs within microbial DNA detected by toll-like receptor 9 are responsible for the favorable properties of CpG oligodeoxynucleotides (ODN) as immune modulators. In this study, mature antigen-pulsed DC or peritumoral injections of CpG ODN, both effective for the treatment of small established tumors, were almost ineffective against large established tumors (1-cm diameter) in a syngeneic murine colon carcinoma model. For large tumors, the antitumor activity of mature antigen-pulsed DC was strongly increased by coinjection of CpG ODN, resulting in a transient control of tumor growth. Rejection of large tumors and long-term cure of mice was achieved by combining injection of antigen-pulsed DC plus CpG ODN at a site distant to the tumor with peritumoral injections of CpG ODN. Depletion of CD8 T cells abrogated the therapeutic activity. Large numbers of DEC-205-positive DC infiltrated the tumor in treated mice. Therapy with 5-fluorouracil and leucovorin was unable to control tumors of the same size. In conclusion, we demonstrate that the immune system, provided that appropriate stimulation with DC and CpG ODN is given, has the potential to cure animals of large solid tumors in situations where even chemotherapy is not efficient.

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