Evidence map›Paper›PMID 27058824›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2016

Development of Third-generation Cocal Envelope Producer Cell Lines for Robust Lentiviral Gene Transfer into Hematopoietic Stem Cells and T-cells.

Olivier Humbert, Don W Gisch, Martin E Wohlfahrt, Amie B Adams, Phil D Greenberg, Tom M Schmitt, Grant D Trobridge, Hans-Peter Kiem

Abstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
–field-weighted citation impact
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

33 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Humanized extracellular vesicles for efficient RNA delivery.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  5. Review
  6. Article
  7. Humanized Extracellular Vesicles for Efficient RNA Delivery.bioRxiv : the preprint server for biology · 2025
    Article
  8. Review
  9. Article
  10. Review
  11. CD90-targeted lentiviral vectors for HSC gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2023
    Article
  12. Article
  13. A CRISPR screen of HIV dependency factors revealsbioRxiv : the preprint server for biology · 2023
    Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. HIV-1-Infected CD4Journal of immunology (Baltimore, Md. : 1950) · 2022
    Article
  20. 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

8 authors.

Olivier HumbertClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Don W GischClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Martin E WohlfahrtClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Amie B AdamsClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Phil D GreenbergClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Tom M SchmittClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Grant D TrobridgeDepartment of Pharmaceutical Sciences, Washington State University, Spokane, Washington, USA.
Hans-Peter KiemClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

Funding

VIRUS-MEDIATED MYELOSUPPRESSIONP01CA018029 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Geoffrey Roger HILL · 1985 to 2026
$128.4M
CORE--VECTOR PRODUCTIONP30DK056465 · NIDDK · FRED HUTCHINSON CANCER RESEARCH CENTER · PI HEIMFELD, SHELLY · 1999 to 2014
$14.9M
Vector ProductionP01AI097100 · NIAID · SEATTLE CHILDREN'S HOSPITAL · PI BEARD, BRIAN C · 2012 to 2016
$11.9M
Stem Cell and Transplantation BiologyU54DK106829 · NIDDK · FRED HUTCHINSON CANCER RESEARCH CENTER · PI DEREK L STIREWALT · 2015 to 2026
$9.1M
Engraftment and in vivo selection of HIV-protected stem cellsR01HL116217 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI KIEM, HANS-PETER · 2012 to 2017
$3.8M
Improved Foamy Virus Vectors for AIDS Gene TherapyR01AI102672 · NIAID · WASHINGTON STATE UNIVERSITY · PI TROBRIDGE, GRANT D · 2013 to 2017
$1.8M
NCI NIH HHS P01 CA018029NHLBI NIH HHS R01 HL116217NIAID NIH HHS P01 AI097100NIAID NIH HHS R01 AI102672NIDDK NIH HHS P30 DK056465NIDDK NIH HHS U54 DK106829
6 · The paper itself

Abstract

Lentiviral vectors (LVs) pseudotyped with vesicular stomatitis virus envelope glycoprotein (VSV-G) have demonstrated great promise in gene therapy trials employing hematopoietic stem cell and T-cells. The VSV-G envelope confers broad tropism and stability to the vector but is toxic when constitutively expressed, which has impeded efforts to generate stable producer cell lines. We previously showed that cocal pseudotyped LVs offer an excellent alternative to VSV-G vectors because of their broad tropism and resistance to human serum inactivation. In this study, we demonstrate that cocal LVs transduce CD34(+) and CD4(+) T-cells more efficiently than VSV-G LVs and share the same receptor(s) for cell entry. 293T-cells stably expressing the cocal envelope produced significantly higher LV titers than VSV-G expressing cells. We developed cocal pseudotyped, third-generation, self-inactivating LV producer cell lines for a GFP reporter and for a WT1 tumor-specific T-cell receptor, which achieved concentrated titers above 10(8) IU/ml and were successfully adapted for growth in suspension, serum-free culture. The resulting LVs were at least as effective as standard LVs in transducing CD34(+) and CD4(+) T-cells. Our stable cocal LV producer cell lines should facilitate the production of large-scale, high titer clinical grade vectors.

Indexed as

Transduction, GeneticCell Culture TechniquesGene ExpressionGenes, ReporterGenetic EngineeringGenetic VectorsHEK293 CellsHematopoietic Stem CellsHumansLentivirusMembrane GlycoproteinsReceptors, LDLReceptors, VirusT-LymphocytesTransgenesVesicular stomatitis Indiana virusglycoprotein G, Cocal virusMembrane GlycoproteinsReceptors, LDLReceptors, VirusViral Envelope Proteins

Identifiers

PMID27058824
PMCPMC5088759

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.