PMID- 28153097
OWN - NLM
STAT- MEDLINE
DCOM- 20170606
LR  - 20240210
IS  - 1525-0024 (Electronic)
IS  - 1525-0016 (Print)
IS  - 1525-0016 (Linking)
VI  - 25
IP  - 2
DP  - 2017 Feb 1
TI  - Dendritic Cells Cross-Present Immunogenic Lentivector-Encoded Antigen from 
      Transduced Cells to Prime Functional T Cell Immunity.
PG  - 504-511
LID - S1525-0016(16)45384-0 [pii]
LID - 10.1016/j.ymthe.2016.11.001 [doi]
AB  - Recombinant lentiviral vectors (LVs) are highly effective vaccination vehicles 
      that elicit protective T cell immunity in disease models. Dendritic cells (DCs) 
      acquire antigen at sites of vaccination and migrate to draining lymph nodes, 
      where they prime vaccine-specific T cells. The potency with which LVs activate 
      CD8(+) T cell immunity has been attributed to the transduction of DCs at the 
      immunization site and durable presentation of LV-encoded antigens. However, it is 
      not known how LV-encoded antigens continue to be presented to T cells once 
      directly transduced DCs have turned over. Here, we report that LV-encoded antigen 
      is efficiently cross-presented by DCs in vitro. We have further exploited the 
      temporal depletion of DCs in the murine CD11c.DTR (diphtheria toxin receptor) 
      model to demonstrate that repopulating DCs that were absent at the time of 
      immunization cross-present LV-encoded antigen to T cells in vivo. Indirect 
      presentation of antigen from transduced cells by DCs is sufficient to prime 
      functional effector T cells that control tumor growth. These data suggest that 
      DCs cross-present immunogenic antigen from LV-transduced cells, thereby 
      facilitating prolonged activation of T cells in the absence of circulating LV 
      particles. These are findings that may impact on the future design of LV 
      vaccination strategies.
CI  - Copyright (c) 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Hotblack, Alastair
AU  - Hotblack A
AD  - Institute for Immunity and Transplantation, University College London, London NW3 
      2PF, UK.
FAU - Seshadri, Sara
AU  - Seshadri S
AD  - Institute for Immunity and Transplantation, University College London, London NW3 
      2PF, UK; Cancer Institute, University College London, London WC1E 6DD, UK.
FAU - Zhang, Lei
AU  - Zhang L
AD  - Institute for Immunity and Transplantation, University College London, London NW3 
      2PF, UK; Cancer Institute, University College London, London WC1E 6DD, UK.
FAU - Hamrang-Yousefi, Sahar
AU  - Hamrang-Yousefi S
AD  - Institute for Immunity and Transplantation, University College London, London NW3 
      2PF, UK; Cancer Institute, University College London, London WC1E 6DD, UK.
FAU - Chakraverty, Ronjon
AU  - Chakraverty R
AD  - Institute for Immunity and Transplantation, University College London, London NW3 
      2PF, UK; Cancer Institute, University College London, London WC1E 6DD, UK.
FAU - Escors, David
AU  - Escors D
AD  - Immunomodulation Group, Navarrabiomed-Fundacion Miguel Servet, Calle de 
      Irunlarrea 3, 31008 Pamplona, Spain.
FAU - Bennett, Clare L
AU  - Bennett CL
AD  - Institute for Immunity and Transplantation, University College London, London NW3 
      2PF, UK; Cancer Institute, University College London, London WC1E 6DD, UK. 
      Electronic address: c.bennett@ucl.ac.uk.
LA  - eng
GR  - 20265/CRUK_/Cancer Research UK/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Ther
JT  - Molecular therapy : the journal of the American Society of Gene Therapy
JID - 100890581
RN  - 0 (Antigens)
RN  - 0 (Biomarkers)
RN  - 0 (CD11c Antigen)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Heparin-binding EGF-like Growth Factor)
RN  - 0 (Vaccines)
SB  - IM
MH  - Animals
MH  - *Antigen Presentation
MH  - Antigens/genetics/*immunology
MH  - Biomarkers
MH  - CD11c Antigen/metabolism
MH  - Cancer Vaccines/immunology
MH  - Coculture Techniques
MH  - Cross-Priming/*immunology
MH  - Dendritic Cells/*immunology/metabolism
MH  - Genetic Vectors/genetics
MH  - Heparin-binding EGF-like Growth Factor/immunology
MH  - *Immunity, Cellular
MH  - Lentivirus/genetics
MH  - Lymph Nodes/immunology/metabolism
MH  - Mice
MH  - Models, Animal
MH  - Neoplasms/immunology/pathology/therapy
MH  - T-Lymphocytes/*immunology/*metabolism
MH  - Transduction, Genetic
MH  - Vaccines/genetics/immunology
PMC - PMC5368353
OTO - NOTNLM
OT  - dendritic cells
OT  - lentivectors
OT  - vaccination
EDAT- 2017/02/06 06:00
MHDA- 2017/06/07 06:00
PMCR- 2017/02/22
CRDT- 2017/02/04 06:00
PHST- 2016/07/05 00:00 [received]
PHST- 2016/11/10 00:00 [revised]
PHST- 2016/11/11 00:00 [accepted]
PHST- 2017/02/04 06:00 [entrez]
PHST- 2017/02/06 06:00 [pubmed]
PHST- 2017/06/07 06:00 [medline]
PHST- 2017/02/22 00:00 [pmc-release]
AID - S1525-0016(16)45384-0 [pii]
AID - 10.1016/j.ymthe.2016.11.001 [doi]
PST - ppublish
SO  - Mol Ther. 2017 Feb 1;25(2):504-511. doi: 10.1016/j.ymthe.2016.11.001.