PMID- 14502218
OWN - NLM
STAT- MEDLINE
DCOM- 20031106
LR  - 20191210
IS  - 0969-7128 (Print)
IS  - 0969-7128 (Linking)
VI  - 10
IP  - 22
DP  - 2003 Oct
TI  - Dendritic cells transduced with gp100 gene by RGD fiber-mutant adenovirus vectors 
      are highly efficacious in generating anti-B16BL6 melanoma immunity in mice.
PG  - 1891-902
AB  - Dendritic cells (DCs) are the most potent professional antigen-presenting cells 
      for the initiation of antigen-specific immune responses, and antigen-loaded DCs 
      have been regarded as promising vaccines in cancer immunotherapy. We previously 
      demonstrated that RGD fiber-mutant adenovirus vector (AdRGD) could attain highly 
      efficient gene transduction into human and murine DCs. The aim of the present 
      study is to demonstrate the predominance of ex vivo genetic DC manipulation using 
      AdRGD in improving the efficacy of DC-based immunotherapy targeting gp100, a 
      melanoma-associated antigen (MAA). Vaccination with murine bone marrow-derived 
      DCs transduced with AdRGD encoding gp100 (AdRGD-gp100/mBM-DCs) dramatically 
      improved resistance to B16BL6 melanoma challenge and pulmonary metastasis as 
      compared with immunization with conventional Ad-gp100-transduced mBM-DCs. The 
      improvement in antimelanoma effects upon immunization with AdRGD-gp100/mBM-DCs 
      correlated with enhanced cytotoxic activities of natural killer (NK) cells and 
      B16BL6-specific cytotoxic T lymphocytes (CTLs). Furthermore, in vivo depletion 
      analysis demonstrated that CD8(+) CTLs and NK cells were the predominant effector 
      cells responsible for the anti-B16BL6 immunity induced by vaccination with 
      AdRGD-gp100/mBM-DCs, and that helper function of CD4(+) T cells was necessary for 
      sufficiently eliciting effector activity. These findings clearly revealed that 
      highly efficient MAA gene transduction to DCs by AdRGD could greatly improve the 
      efficacy of DC-based immunotherapy against melanoma.
FAU - Okada, N
AU  - Okada N
AD  - Department of Biopharmaceutics, Kyoto Pharmaceutical University, Kyoto, Japan.
FAU - Masunaga, Y
AU  - Masunaga Y
FAU - Okada, Y
AU  - Okada Y
FAU - Mizuguchi, H
AU  - Mizuguchi H
FAU - Iiyama, S
AU  - Iiyama S
FAU - Mori, N
AU  - Mori N
FAU - Sasaki, A
AU  - Sasaki A
FAU - Nakagawa, S
AU  - Nakagawa S
FAU - Mayumi, T
AU  - Mayumi T
FAU - Hayakawa, T
AU  - Hayakawa T
FAU - Fujita, T
AU  - Fujita T
FAU - Yamamoto, A
AU  - Yamamoto A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Gene Ther
JT  - Gene therapy
JID - 9421525
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Oligopeptides)
RN  - 0 (PMEL protein, human)
RN  - 0 (Pmel protein, mouse)
RN  - 0 (gp100 Melanoma Antigen)
RN  - 78VO7F77PN (arginyl-glycyl-aspartic acid)
SB  - IM
MH  - Adenoviridae/genetics
MH  - Animals
MH  - Dendritic Cells/*immunology
MH  - Female
MH  - Genetic Therapy/*methods
MH  - Genetic Vectors/administration & dosage/genetics
MH  - Humans
MH  - Immunotherapy, Adoptive/*methods
MH  - Killer Cells, Natural/immunology
MH  - Lung Neoplasms/immunology/*secondary/therapy
MH  - Melanoma, Experimental/immunology/*therapy
MH  - Membrane Glycoproteins/*genetics
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Nude
MH  - Mutation
MH  - Neoplasm Proteins/*genetics
MH  - Oligopeptides/genetics
MH  - Skin Neoplasms/immunology/*therapy
MH  - T-Lymphocytes, Cytotoxic/immunology
MH  - Transduction, Genetic/methods
MH  - gp100 Melanoma Antigen
EDAT- 2003/09/23 05:00
MHDA- 2003/11/07 05:00
CRDT- 2003/09/23 05:00
PHST- 2003/09/23 05:00 [pubmed]
PHST- 2003/11/07 05:00 [medline]
PHST- 2003/09/23 05:00 [entrez]
AID - 3302090 [pii]
AID - 10.1038/sj.gt.3302090 [doi]
PST - ppublish
SO  - Gene Ther. 2003 Oct;10(22):1891-902. doi: 10.1038/sj.gt.3302090.