Evidence map›Paper›PMID 18496571›Full record

ArticleGene therapy2008

Development of optimal bicistronic lentiviral vectors facilitates high-level TCR gene expression and robust tumor cell recognition.

S Yang, C J Cohen, P D Peng, Y Zhao, L Cassard, Z Yu, Z Zheng, S Jones, N P Restifo, S A Rosenberg and 1 more

Open access · greenAbstract read
In one paragraph

Article in Gene therapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.

0numbers the graph read from it
0cells of the map it votes in
113citing papers in PubMed
8.4field-weighted citation impact, top 2% 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

113 citing papers in PubMed, 181 citations in OpenAlex.

  1. Development of human anti-murine T-cell receptor antibodies in both responding and nonresponding patients enrolled in TCR gene therapy trials.Clinical cancer research : an official journal of the American Association for Cancer Research · 2010
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  8. A single dose of a vectorized mAb targeting TDP-43 potently inhibits the neuropathology in a model of ALS/FTD.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
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  17. Review
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53 more citing papers are in PubMed but not listed here.

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

11 authors at 3 institutions in 1 country.

S YangSurgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
C J Cohen
P D Peng
Y Zhao
L Cassard
Z Yu
Z Zheng
S Jones
N P Restifo
S A Rosenberg
R A Morgan
Center for Cancer Research · USNational Institutes of Health · USNational Cancer Institute · US

Funding

Gene therapy of cancerZIABC010985 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI ROSENBERG, STEVEN · 2009 to 2025
$56.8M
Building on the success of the adoptive immunotherapy of cancerZIABC010763 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI ROSENBERG, STEVEN · 2009 to 2020
$25.0M
SURGICAL CONSULTATIONS AND COLLABORATIVE RESEARCH IN SURGICAL SERVICES AT NIHZ01SC003800 · SC · DIVISION OF CLINICAL SCIENCES - NCI · PI ROSENBERG, STEVEN A · 1996 to 2008
$7.5M
THE IMMUNOTHERAPY OF ANIMAL AND HUMAN CANCERZ01SC003811 · SC · CLINICAL SCIENCES · PI ROSENBERG, STEVEN A · 1996 to 2007
$3.2M
Adoptive Cell Transfer Immunotherapy of CancerZ01BC010984 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI ROSENBERG, STEVEN · 2008 to 2008
$1.5M
Intramural NIH HHS Z01 SC003811
6 · The paper itself

Abstract

In human gene therapy applications, lentiviral vectors may have advantages over gamma-retroviral vectors in several areas, including the ability to transduce nondividing cells, resistance to gene silencing and a potentially safer integration site profile. However, unlike gamma-retroviral vectors it has been problematic to drive the expression of multiple genes efficiently and coordinately with approaches such as internal ribosome entry sites or dual promoters. Using different 2A peptides, lentiviral vectors expressing two-gene T-cell receptors directed against the melanoma differentiation antigens gp100 and MART-1 were constructed. We demonstrated that addition of amino-acid spacer sequences (GSG or SGSG) before the 2A sequence is a prerequisite for efficient synthesis of biologically active T-cell receptors and that addition of a furin cleavage site followed by a V5 peptide tag yielded optimal T-cell receptor gene expression. Furthermore, we determined that the furin cleavage site was recognized in lymphocytes and accounted for removal of residual 2A peptides at the post-translational level with an efficiency of 20-30%, which could not be increased by addition of multiple furin cleavage sites. The novel bicistronic lentiviral vector developed herein afforded robust anti-melanoma activities to engineered peripheral blood lymphocytes, including cytokine secretion, cell proliferation and lytic activity. Such optimal vectors may have immediate applications in cancer gene therapy.

Indexed as

Genes, T-Cell ReceptorAntigens, NeoplasmCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell Line, TumorFurinGenetic EngineeringGenetic TherapyGenetic Vectorsgp100 Melanoma AntigenHumansImmunotherapy, AdoptiveLentivirusLymphocytes, Tumor-InfiltratingMART-1 AntigenMelanomaAntigens, NeoplasmFuringp100 Melanoma AntigenMART-1 AntigenMembrane GlycoproteinsMLANA protein, humanNeoplasm ProteinsPMEL protein, humanReceptors, Antigen, T-Cell

Identifiers

PMID18496571
PMCPMC2684456
OpenAlexW1977917700

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.