PMID- 12450042
OWN - NLM
STAT- MEDLINE
DCOM- 20021213
LR  - 20121115
IS  - 0022-3085 (Print)
IS  - 0022-3085 (Linking)
VI  - 97
IP  - 5
DP  - 2002 Nov
TI  - Administration of interleukin-12 and -18 enhancing the antitumor immunity of 
      genetically modified dendritic cells that had been pulsed with Semliki forest 
      virus-mediated tumor complementary DNA.
PG  - 1184-90
AB  - OBJECT: Immunogene therapy for malignant gliomas was further investigated in this 
      study to improve its therapeutic efficacy. METHODS: Dendritic cells (DCs) were 
      isolated from bone marrow and pulsed with phosphate-buffered saline or Semliki 
      Forest virus (SFV)-mediated 203 glioma complementary (c)DNA with or without 
      systemic administration of interleukin (IL)-12 and IL-18 to treat mice bearing 
      the 203 glioma. To study the immune mechanisms involved in tumor regression, the 
      authors investigated tumor growth of an implanted 203 glioma model in T cell 
      subset-depleted mice and in interferon (IFN) gamma-neutralized mice. To examine 
      the protective immunity produced by tumor inoculation, a repeated challenge of 
      203 glioma cells was given by injecting the cells into the left thighs of 
      surviving mice and the growth of these cells was monitored. The authors 
      demonstrated that the combined administration of SFV-cDNA, IL-12, and IL-18 
      produced significant antitumor effects against the growth of murine glioma cells 
      in vivo and also can induce specific antitumor immunity. The synergic effects of 
      the combination of SFV-cDNA, IL-12, and IL-18 in vivo were also observed to 
      coincide with markedly augmented IFN-gamma production. The antitumor effects of 
      this combined therapy are mediated by CD4+ and CD8+ T cells and by NK cells. 
      These results indicate that the use of IL-18 and IL-12 in DC-based immunotherapy 
      for malignant glioma is beneficial. CONCLUSIONS: Immunogene therapy combined with 
      DC therapy, IL-12, and IL-18 may be an excellent candidate in the development of 
      a new treatment protocol. The self-replicating SFV system may therefore provide a 
      novel approach for the treatment of malignant gliomas.
FAU - Yamanaka, Ryuya
AU  - Yamanaka R
AD  - Clinical Gene Therapy Branch, National Human Genome Research Institute, National 
      Institutes of Health, Bethesda, Maryland, USA. ryaman@pop11.odn.ne.jp
FAU - Yajima, Naoki
AU  - Yajima N
FAU - Tsuchiya, Naoto
AU  - Tsuchiya N
FAU - Honma, Junpei
AU  - Honma J
FAU - Tanaka, Ryuichi
AU  - Tanaka R
FAU - Ramsey, Jay
AU  - Ramsey J
FAU - Blaese, Michael
AU  - Blaese M
FAU - Xanthopoulos, Kleanthis G
AU  - Xanthopoulos KG
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Neurosurg
JT  - Journal of neurosurgery
JID - 0253357
RN  - 0 (DNA, Complementary)
RN  - 0 (DNA, Neoplasm)
RN  - 0 (Interleukin-18)
RN  - 187348-17-0 (Interleukin-12)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Antibody Formation/physiology
MH  - CD4-Positive T-Lymphocytes/physiology
MH  - CD8-Positive T-Lymphocytes/physiology
MH  - DNA, Complementary/therapeutic use
MH  - DNA, Neoplasm/therapeutic use
MH  - Dendritic Cells/physiology
MH  - *Genetic Therapy
MH  - Genetic Vectors
MH  - Glioma/genetics/immunology/*therapy
MH  - *Immunotherapy
MH  - Interferon-gamma/physiology
MH  - Interleukin-12/*therapeutic use
MH  - Interleukin-18/*therapeutic use
MH  - Killer Cells, Natural/physiology
MH  - Mice
MH  - Semliki forest virus/genetics
MH  - T-Lymphocytes, Cytotoxic/physiology
MH  - Tumor Cells, Cultured
EDAT- 2002/11/27 04:00
MHDA- 2002/12/17 04:00
CRDT- 2002/11/27 04:00
PHST- 2002/11/27 04:00 [pubmed]
PHST- 2002/12/17 04:00 [medline]
PHST- 2002/11/27 04:00 [entrez]
AID - 10.3171/jns.2002.97.5.1184 [doi]
PST - ppublish
SO  - J Neurosurg. 2002 Nov;97(5):1184-90. doi: 10.3171/jns.2002.97.5.1184.