PMID- 11133750
OWN - NLM
STAT- MEDLINE
DCOM- 20010215
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 97
IP  - 1
DP  - 2001 Jan 1
TI  - Lentivirus-transduced human monocyte-derived dendritic cells efficiently 
      stimulate antigen-specific cytotoxic T lymphocytes.
PG  - 114-21
AB  - Dendritic cells (DCs) are professional antigen-presenting cells that are highly 
      effective adjuvants for immunizing against pathogens and tumor antigens. The 
      potential merit of genetic approaches to loading DCs with antigens is to express 
      high and sustained levels of proteins that can be subsequently processed and 
      presented to T lymphocytes. Replication-defective oncoretroviruses are able to 
      efficiently transduce CD34(+) progenitor-derived DCs but not monocyte-derived 
      DCs. Here, it is shown that efficient gene transfer is obtained using a human 
      immunodeficiency virus-1-derived lentiviral vector deleted of all structural and 
      accessory genes. Infection of immature DCs with the lentiviral vector at a 
      multiplicity of infection of 20 resulted in stable gene expression in 30% to 40% 
      of the matured DCs. Proviral DNA was detectable by Alu polymerase chain reaction 
      for the lentiviral but not the oncoretroviral vector. Most importantly, it is 
      demonstrated that lentivirus-transduced DCs were fully functional and effectively 
      activated autologous HLA A2.1(+) peripheral blood cytotoxic T lymphocytes (CTLs). 
      DCs expressing lentiviral vector-encoded Flu peptide were at least as efficient 
      as DCs pulsed with the same peptide in stimulating specific CTLs. The efficacy of 
      the lentivirus-transduced DCs was further demonstrated by their ability to 
      directly activate freshly harvested peripheral blood Flu-specific CTLs in the 
      absence of CD4(+) T-cell help and exogenous cytokines. The availability of a 
      stable gene delivery system based on a multiply attenuated lentivirus that does 
      not encode any viral protein and that allows sustained antigen presentation by 
      DCs derived from blood monocytes will be very useful for the biologic 
      investigation of DCs and the improvement of immunotherapeutic strategies 
      involving DCs.
FAU - Dyall, J
AU  - Dyall J
AD  - Department of Human Genetics, the Gene Transfer and Somatic Cell Engineering 
      Facility and the Immunology Program, Memorial Sloan-Kettering Cancer Center, New 
      York, NY 10021, USA.
FAU - Latouche, J B
AU  - Latouche JB
FAU - Schnell, S
AU  - Schnell S
FAU - Sadelain, M
AU  - Sadelain M
LA  - eng
GR  - P01CA59350/CA/NCI NIH HHS/United States
GR  - P01CA65930/CA/NCI NIH HHS/United States
GR  - R01HL56712/HL/NHLBI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (DNA, Viral)
RN  - 0 (Epitopes)
RN  - 0 (Peptide Fragments)
RN  - 0 (Viral Matrix Proteins)
RN  - 0 (influenza virus membrane protein (58-66))
SB  - IM
MH  - CD4-Positive T-Lymphocytes
MH  - Cell Differentiation
MH  - Cytotoxicity Tests, Immunologic
MH  - DNA, Viral/metabolism
MH  - Dendritic Cells/cytology/drug effects/*immunology
MH  - Epitopes
MH  - Genetic Vectors/pharmacology/standards
MH  - Humans
MH  - Lentivirus/*genetics
MH  - Monocytes/cytology
MH  - Peptide Fragments/immunology/pharmacology
MH  - T-Lymphocytes, Cytotoxic/drug effects/*immunology
MH  - Transduction, Genetic/*methods/standards
MH  - Viral Matrix Proteins/immunology/pharmacology
EDAT- 2001/01/03 11:00
MHDA- 2001/03/03 10:01
CRDT- 2001/01/03 11:00
PHST- 2001/01/03 11:00 [pubmed]
PHST- 2001/03/03 10:01 [medline]
PHST- 2001/01/03 11:00 [entrez]
AID - S0006-4971(20)48116-9 [pii]
AID - 10.1182/blood.v97.1.114 [doi]
PST - ppublish
SO  - Blood. 2001 Jan 1;97(1):114-21. doi: 10.1182/blood.v97.1.114.