PMID- 12874015
OWN - NLM
STAT- MEDLINE
DCOM- 20030813
LR  - 20210103
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 63
IP  - 14
DP  - 2003 Jul 15
TI  - Dendritic cells stimulated with a bacterial product, OK-432, efficiently induce 
      cytotoxic T lymphocytes specific to tumor rejection peptide.
PG  - 4112-8
AB  - Dendritic cells (DCs) are potent antigen-presenting cells, which have recently 
      been applied for cancer immunotherapy using epitope peptides. Accumulating 
      results of the clinical trials of such a strategy suggest that maturity of the 
      applied DCs has a significant impact on the outcome of the vaccination. Here we 
      examined the effects of penicillin-killed Streptococcus pyogenes (OK-432) on DC 
      maturation and functions including induction of CTLs. DCs generated from 
      peripheral blood using granulocyte macrophage colony-stimulating factor and 
      interleukin (IL)-4 showed immunophenotypes consistent with immature DCs (iDCs). 
      These iDCs were further incubated with medium alone, tumor necrosis factor alpha, 
      lipopolysaccharide, or OK-432. The immunophenotypical analysis showed DCs 
      stimulated with OK-432 (OK-DCs) possessed significantly higher expression of CD83 
      compared with unstimulated DCs. Furthermore, OK-DCs showed significantly higher 
      production of IL-12 and IFN-gamma compared with DCs with other stimulations. 
      These results indicate that OK-432 stimulates iDCs to have a mature phenotype and 
      to produce a significant amount of T-helper 1-type cytokines. To examine the 
      potency of OK-DCs on the induction of specific CTLs, the tumor rejection peptide 
      derived from carcinoembryonic antigen was used as a model antigen. The 
      HLA-tetramer assay showed that potent CTL was induced with OK-DCs at high 
      frequency. These results indicate that OK-432 efficiently stimulates DCs without 
      interfering with the presentation of pulsed peptide. Furthermore, OK-432 does not 
      activate nuclear factor kappaB through Toll-like receptor 2 or Toll-like receptor 
      4 in the indicator cell system; however, it induces IL-12 production through the 
      beta(2) integrin system on DCs. These results strongly suggest that OK-432 could 
      be applied to develop an efficient cancer vaccine using DCs pulsed with tumor 
      rejection peptides.
FAU - Nakahara, Saori
AU  - Nakahara S
AD  - Department of Surgery and Bioengineering, Institute of Medical Science, The 
      University of Tokyo, Tokyo 108-8639, Japan.
FAU - Tsunoda, Takuya
AU  - Tsunoda T
FAU - Baba, Toshiyuki
AU  - Baba T
FAU - Asabe, Shinichi
AU  - Asabe S
FAU - Tahara, Hideaki
AU  - Tahara H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (CD18 Antigens)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (TLR2 protein, human)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Toll-Like Receptors)
RN  - 130068-27-8 (Interleukin-10)
RN  - 187348-17-0 (Interleukin-12)
RN  - 39325-01-4 (Picibanil)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - CD18 Antigens/metabolism
MH  - Dendritic Cells/drug effects/*immunology/metabolism
MH  - Epitopes, T-Lymphocyte/immunology
MH  - Humans
MH  - Interferon-gamma/biosynthesis/metabolism
MH  - Interleukin-10/biosynthesis
MH  - Interleukin-12/biosynthesis/metabolism
MH  - Membrane Glycoproteins/immunology/metabolism
MH  - Picibanil/*pharmacology
MH  - Receptors, Cell Surface/immunology/metabolism
MH  - Signal Transduction
MH  - T-Lymphocytes, Cytotoxic/*immunology
MH  - Toll-Like Receptor 2
MH  - Toll-Like Receptor 4
MH  - Toll-Like Receptors
EDAT- 2003/07/23 05:00
MHDA- 2003/08/14 05:00
CRDT- 2003/07/23 05:00
PHST- 2003/07/23 05:00 [pubmed]
PHST- 2003/08/14 05:00 [medline]
PHST- 2003/07/23 05:00 [entrez]
PST - ppublish
SO  - Cancer Res. 2003 Jul 15;63(14):4112-8.