PMID- 12939642
OWN - NLM
STAT- MEDLINE
DCOM- 20031106
LR  - 20191003
IS  - 0969-7128 (Print)
IS  - 1476-5462 (Electronic)
IS  - 0969-7128 (Linking)
VI  - 10
IP  - 20
DP  - 2003 Sep
TI  - Biased epitope selection by recombinant vaccinia-virus (rVV)-infected mature or 
      immature dendritic cells.
PG  - 1754-65
AB  - Recombinant expression vectors represent a powerful way to deliver whole antigens 
      (Ags) for immunization. Sustained Ag expression in vector-infected dendritic 
      cells (DC) combines Ag-specific stimulation with powerful costimulation and, 
      simultaneously, through 'self-selection' of ad hoc epitopes broadens the scope of 
      immunization beyond restrictions posed by individual patients' human leukocyte 
      antigen (HLA) phenotype. In this study, therefore, we evaluated the efficiency of 
      a recombinant vaccinia virus encoding the gp100/PMel17 melanoma Ag (rVV-gp100) to 
      infect immature (iDC) or mature dendritic cells (mDC) derived from circulating 
      mononuclear cells and the effect of infection on their status of maturation. In 
      addition, we tested the ability of rVV-gp100-infected iDC and mDC to present the 
      HLA-A*0201-associated gp100:209-217 epitope (g209). Irrespective of status of 
      maturation, rVV-gp100 infection induced gp100 expression while only partially 
      reversing the expression of some maturation markers. However, endogenous 
      presentation of the wild-type g209 epitope was inefficient. The low efficiency 
      was epitope-specific since infection of DC with rVV encoding a gp100 construct 
      containing the modified gp100:209-217 (210M) (g209-2M) epitope characterized by 
      high binding affinity for HLA-A*0201 restored efficient Ag presentation. 
      Presentation of an HLA-class II-associated epitope and cytokine release by DC was 
      not altered by rVV infection. Thus, Ag expression driven by rVV may be an 
      efficient strategy for whole Ag delivery. However, since the effectiveness of Ag 
      processing and presentation is subject to stringent HLA/epitope pairing, and for 
      other yet undefined rules, the assumption that whole Ag delivery may circumvent 
      HLA restriction is incorrect and recombinant expression vectors encoding 
      well-characterized polyepitopic constructs may prove more effective.
FAU - Nagorsen, D
AU  - Nagorsen D
AD  - Immunogenetics Section, Department of Transfusion Medicine, Clinical Center, 
      National Institutes of Health, Bethesda, MD 20892, USA.
FAU - Panelli, M
AU  - Panelli M
FAU - Dudley, M E
AU  - Dudley ME
FAU - Finkelstein, S E
AU  - Finkelstein SE
FAU - Rosenberg, S A
AU  - Rosenberg SA
FAU - Marincola, F M
AU  - Marincola FM
LA  - eng
GR  - Z01 SC003811-32/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Gene Ther
JT  - Gene therapy
JID - 9421525
RN  - 0 (Cancer Vaccines)
RN  - 0 (Epitopes)
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-A*02:01 antigen)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (PMEL protein, human)
RN  - 0 (Peptides)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (g209-2M melanoma peptide)
RN  - 0 (gp100 Melanoma Antigen)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Antigen Presentation
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - Cancer Vaccines
MH  - Cell Line
MH  - Clone Cells
MH  - Dendritic Cells/*immunology
MH  - Epitopes/*immunology
MH  - Flow Cytometry
MH  - Genetic Therapy/*methods
MH  - Genetic Vectors/*administration & dosage
MH  - HLA-A Antigens/*immunology
MH  - HLA-A2 Antigen
MH  - Humans
MH  - Interferon-gamma/immunology
MH  - Melanoma/immunology/therapy
MH  - Membrane Glycoproteins/genetics
MH  - Neoplasm Proteins/genetics
MH  - Peptides
MH  - Receptors, Antigen, T-Cell/immunology
MH  - Vaccinia virus/*genetics
MH  - gp100 Melanoma Antigen
PMC - PMC2275329
MID - NIHMS42591
EDAT- 2003/08/27 05:00
MHDA- 2003/11/07 05:00
PMCR- 2008/03/26
CRDT- 2003/08/27 05:00
PHST- 2003/08/27 05:00 [pubmed]
PHST- 2003/11/07 05:00 [medline]
PHST- 2003/08/27 05:00 [entrez]
PHST- 2008/03/26 00:00 [pmc-release]
AID - 3302066 [pii]
AID - 10.1038/sj.gt.3302066 [doi]
PST - ppublish
SO  - Gene Ther. 2003 Sep;10(20):1754-65. doi: 10.1038/sj.gt.3302066.