Evidence map›Paper›PMID 16136165›Full record

ArticleGene therapy2006

Enhanced transduction of mouse bone marrow-derived dendritic cells by repetitive infection with self-complementary adeno-associated virus 6 combined with immunostimulatory ligands.

W A Aldrich, C Ren, A F White, S-Z Zhou, S Kumar, C B Jenkins, D R Shaw, T V Strong, P L Triozzi, S Ponnazhagan

Abstract read
PubMed Publisher
In one paragraph

Article in Gene therapy, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.2field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 36 citations in OpenAlex.

  1. Review
  2. Review
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  4. Muscle-Directed Delivery of an AAV1 Vector Leads to Capsid-Specific T Cell Exhaustion in Nonhuman Primates and Humans.Molecular therapy : the journal of the American Society of Gene Therapy · 2020
    Article
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  16. Article
  17. The role of the adeno-associated virus capsid in gene transfer.Methods in molecular biology (Clifton, N.J.) · 2008
    Review
  18. Article
  19. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

W A AldrichDepartment of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA.
C Ren
A F White
S-Z Zhou
S Kumar
C B Jenkins
D R Shaw
T V Strong
P L Triozzi
S Ponnazhagan
University of Alabama at Birmingham · USEpigen Biosciences (United States) · US

Funding

UAB Rexinoids for Breast Cancer PreventionP50CA089019 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI GRIZZLE, WILLIAM E. · 2000 to 2011
$26.0M
Gene Therapy for Prostate CancerR01CA098817 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI PONNAZHAGAN, SELVARANGAN · 2003 to 2007
$1.3M
Novel dendritic cell therapy for human cancersR01CA090850 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI PONNAZHAGAN, SELVARANGAN · 2002 to 2005
$954k
NCI NIH HHS P50 CA89019NCI NIH HHS R01CA90850NCI NIH HHS R01CA98817
6 · The paper itself

Abstract

The potential of adeno-associated virus (AAV)-based vectors in human gene therapy is being explored for several diseases. Although sustained transgene expression and low vector-associated cellular immunity are attractive features of recombinant (r) AAV, the wider application of rAAV vectors encapsidated in serotype 2 capsid is hampered by poor transduction efficiency in many target tissues. These include ex vivo-generated dendritic cells (DC), which have demonstrated promising immunotherapeutic activity. We report here that efficient transduction of mouse bone marrow-derived DC can be achieved with self-complementary (sc) rAAV encapsidated in serotype 6 capsid. Sequential exposure of DC precursor cultures to IL-4 and GM-CSF with sc rAAV6 encoding the human tumor antigen, carcinoembryonic antigen (CEA), for 7 days followed by activation with CpG oligodeoxynucleotides (ODN) and anti-mouse CD40 antibody resulted in highly efficient transduction of DC. DC surface markers as determined by flow cytometry analysis of sc rAAV6-transduced DC were comparable to nontransduced DC. Efficiency of vector transduction and transgene expression were confirmed by immunostaining and real-time PCR. Microarray analysis of RNA from CpG ODN and CD40 antibody stimulated sc AAV6-transduced DC revealed upregulation of transcription factors and cytokines involved in immune activation and downregulation of inhibitory factors, suggesting a possible role of transcriptional activation in the observed effect. The adoptive transfer into syngeneic mice of the ex vivo-transduced and activated DC resulted in the development of CEA-specific antibody and T-helper 1-associated immune responses. Immunized mice also developed antibody to AAV6 capsid protein, which did not crossreact with AAV2 capsid protein. These studies demonstrate the potential utility of sc rAAV serotype 6-based vectors in transduction of DC for genetic vaccination approaches.

Indexed as

Adoptive TransferAnimalsAntibodies, ViralAntibody SpecificityAntigen PresentationBone Marrow CellsCarcinoembryonic AntigenCD40 AntigensCell LineCpG IslandsDendritic CellsDependovirusEnzyme-Linked Immunosorbent AssayFlow CytometryGene ExpressionGenetic EngineeringAntibodies, ViralCarcinoembryonic AntigenCD40 AntigensGreen Fluorescent ProteinsInterferon-gamma

Identifiers

PMID16136165
OpenAlexW1992823019

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.