Evidence map›Paper›PMID 27138041›Full record

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

Generation of Genetically Engineered Precursor T-Cells From Human Umbilical Cord Blood Using an Optimized Alpharetroviral Vector Platform.

Juwita Hübner, Shahabuddin S Hoseini, Julia D Suerth, Dirk Hoffmann, Marcel Maluski, Jessica Herbst, Holger Maul, Arnab Ghosh, Britta Eiz-Vesper, Qinggong Yuan and 4 more

Open access · hybridAbstract 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 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.0field-weighted citation impact, top 12% 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

14 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Donor T cells for CAR T cell therapy.Biomarker research · 2022
    Review
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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

14 authors at 3 institutions in 2 countries.

Juwita HübnerDepartment of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
Shahabuddin S HoseiniDepartment of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
Julia D SuerthInstitute of Experimental Hematology, Hannover Medical School, Hannover, Germany.
Dirk HoffmannIntegrated Research and Treatment Center Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany.
Marcel MaluskiDepartment of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
Jessica HerbstDepartment of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
Holger MaulDepartment of Gynecology and Obstetrics, Marienkrankenhaus, Hamburg, Germany.
Arnab GhoshDepartment of Immunology and Medicine, Memorial Sloan-Kettering Cancer Center, New York, USA.
Britta Eiz-VesperInstitute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.
Qinggong YuanDepartment of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Michael OttDepartment of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Michael HeuserIntegrated Research and Treatment Center Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany.
Axel SchambachIntegrated Research and Treatment Center Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany.
Martin G SauerDepartment of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
Medizinische Hochschule Hannover · DEMarienkrankenhaus Hamburg · DEMemorial Sloan Kettering Cancer Center · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

Retroviral engineering of hematopoietic stem cell-derived precursor T-cells (preTs) opens the possibility of targeted T-cell transfer across human leukocyte antigen (HLA)-barriers. Alpharetroviral vectors exhibit a more neutral integration pattern thereby reducing the risk of insertional mutagenesis. Cord blood-derived CD34+ cells were transduced and differentiated into preTs in vitro. Two promoters, elongation-factor-1-short-form, and a myeloproliferative sarcoma virus variant in combination with two commonly used envelopes were comparatively assessed choosing enhanced green fluorescent protein or a third-generation chimeric antigen receptor (CAR) against CD123 as gene of interest. Furthermore, the inducible suicide gene iCaspase 9 has been validated. Combining the sarcoma virus-derived promoter with a modified feline endogenous retrovirus envelope glycoprotein yielded in superior transgene expression and transduction rates. Fresh and previously frozen CD34+ cells showed similar transduction and expansion rates. Transgene-positive cells did neither show proliferative impairment nor alteration in their lymphoid differentiation profile. The sarcoma virus-derived promoter only could express sufficient levels of iCaspase 9 to mediate dimerizer-induced apoptosis. Finally, the CD123 CAR was efficiently expressed in CD34+ cells and proved to be functional when expressed on differentiated T-cells. Therefore, the transduction of CD34+ cells with alpharetroviral vectors represents a feasible and potentially safer approach for stem cell-based immunotherapies for cancer.

Indexed as

Genetic EngineeringAlpharetrovirusAntigens, CD34ApoptosisBacterial Outer Membrane ProteinsBiomarkersCell DifferentiationFetal BloodGene ExpressionGenes, ReporterGenetic VectorsGene Transfer TechniquesHematopoietic Stem CellsHumansInterleukin-3 Receptor alpha SubunitPhenotypeAntigens, CD34Bacterial Outer Membrane ProteinsBiomarkersInterleukin-3 Receptor alpha Subunitmembrane protein, 75kDaReceptors, Antigen, T-Cell

Identifiers

PMID27138041
PMCPMC5088766
OpenAlexW2346685799

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.