PMID- 11691812
OWN - NLM
STAT- MEDLINE
DCOM- 20011204
LR  - 20210102
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 61
IP  - 21
DP  - 2001 Nov 1
TI  - Efficient antigen gene transduction using Arg-Gly-Asp fiber-mutant adenovirus 
      vectors can potentiate antitumor vaccine efficacy and maturation of murine 
      dendritic cells.
PG  - 7913-9
AB  - Dendritic cells (DCs), the most effective antigen-presenting cells, are being 
      studied as adjuvants or antigen delivery vehicles for eliciting T-cell-mediated 
      antitumor immunity. Gene delivery to DCs provides an intracellular source of 
      antigen for efficient and persistent loading to MHC class I molecules capable of 
      activating CD8(+) CTLs, which play a central role in antitumor immunity. We 
      previously reported that the fiber-mutant adenovirus vector (Ad) harboring the 
      Arg-Gly-Asp (RGD) sequence in the HI loop of its fiber knob could more 
      efficiently transduce the LacZ gene into both murine DC lines and normal human 
      DCs than conventional Ad. In the present study, we compared immunological 
      properties and vaccine efficacy of DC2.4 cells, an immature murine DC line, 
      transduced with an ovalbumin (OVA) gene by fiber-mutant Ad (Ad-RGD-OVA) or 
      conventional Ad (Ad-OVA). Ad-RGD-OVA-infected DC2.4 cells could more efficiently 
      present OVA peptides via MHC class I molecules in a vector particle-dependent 
      manner and induce OVA-specific CTL response by vaccination than Ad-OVA-infected 
      DC2.4 cells. This result was correlated with the efficiency of gene transduction 
      into DC2.4 cells by both types of Ad. Moreover, vaccination with 
      Ad-RGD-OVA-infected DC2.4 cells could achieve an equal or greater antitumor 
      effect against challenge with E.G7-OVA tumor cells with lower doses of Ad on 
      infection or fewer cells for immunization than the vaccination procedure using 
      Ad-OVA-infected DC2.4 cells. In addition, the maturation of DC2.4 cells was 
      promoted by efficient expression of the antigen gene by the Arg-Gly-Asp 
      fiber-mutant Ad. Flow cytometric analysis indicated enhanced expression of MHC 
      class I and II molecules as well as CD80, CD86, CD40, and CD54, and reverse 
      transcription-PCR analysis revealed increased levels of interleukin 12 p40 mRNA. 
      However, infection by Ad-OVA or Ad that did not contain the cDNA of interest 
      (Ad-Null and Ad-RGD-Null) contributed little to phenotypical changes in DC2.4 
      cells. On the basis of these results, we propose that DC manipulation using the 
      Arg-Gly-Asp fiber-mutant Ad system could advance the development of more 
      effective vaccines and allow for more convenient administration of DC-based gene 
      immunotherapy.
FAU - Okada, N
AU  - Okada N
AD  - Department of Biopharmaceutics, Kyoto Pharmaceutical University, Kyoto 607-8414, 
      Japan. okada@mb.kyoto-phu.ac.jp
FAU - Saito, T
AU  - Saito T
FAU - Masunaga, Y
AU  - Masunaga Y
FAU - Tsukada, Y
AU  - Tsukada Y
FAU - Nakagawa, S
AU  - Nakagawa S
FAU - Mizuguchi, H
AU  - Mizuguchi H
FAU - Mori, K
AU  - Mori K
FAU - Okada, Y
AU  - Okada Y
FAU - Fujita, T
AU  - Fujita T
FAU - Hayakawa, T
AU  - Hayakawa T
FAU - Mayumi, T
AU  - Mayumi T
FAU - Yamamoto, A
AU  - Yamamoto A
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 (Cancer Vaccines)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Luminescent Proteins)
RN  - 0 (Oligopeptides)
RN  - 0 (RNA, Messenger)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - 187348-17-0 (Interleukin-12)
RN  - 78VO7F77PN (arginyl-glycyl-aspartic acid)
RN  - 9006-59-1 (Ovalbumin)
SB  - IM
MH  - Adenoviridae/*genetics/immunology
MH  - Animals
MH  - Antigen Presentation/immunology
MH  - Cancer Vaccines/genetics/*immunology
MH  - Cell Differentiation/physiology
MH  - Dendritic Cells/*immunology/metabolism/physiology
MH  - Female
MH  - Genetic Vectors/genetics
MH  - Green Fluorescent Proteins
MH  - Histocompatibility Antigens Class I/immunology
MH  - Immunotherapy, Adoptive
MH  - Interleukin-12/genetics/immunology
MH  - Luminescent Proteins/genetics
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neoplasms, Experimental/immunology/prevention & control
MH  - Oligopeptides/*genetics/immunology
MH  - Ovalbumin/genetics/immunology
MH  - RNA, Messenger/biosynthesis/genetics
MH  - T-Lymphocytes, Cytotoxic/immunology
MH  - Transduction, Genetic
EDAT- 2001/11/03 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/11/03 10:00
PHST- 2001/11/03 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/11/03 10:00 [entrez]
PST - ppublish
SO  - Cancer Res. 2001 Nov 1;61(21):7913-9.