Evidence map›Paper›PMID 29267342›Full record

ArticlePloS one2017

Adenovirus platform enhances transduction efficiency of human mesenchymal stem cells: An opportunity for cellular carriers of targeted TRAIL-based TR3 biologics in ovarian cancer.

Lindsay M Kuroki, Xingjian Jin, Igor P Dmitriev, Elena A Kashentseva, Matthew A Powell, David G Mutch, Allan B Dietz, David T Curiel, William G Hawkins, Dirk Spitzer

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.0field-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

13 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. Virotherapy as Gene Deliver for Anti-Cancer Therapy: A Review Article.Asian Pacific journal of cancer prevention : APJCP · 2025
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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

10 authors at 2 institutions in 1 country.

Lindsay M KurokiDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, United States of America.
Xingjian JinDepartment of Surgery, Washington University School of Medicine, St. Louis, MO, United States of America.
Igor P DmitrievDepartment of Radiation Oncology and Biological Therapeutics Center, Washington University School of Medicine, St. Louis, MO, United States of America.
Elena A KashentsevaDepartment of Radiation Oncology and Biological Therapeutics Center, Washington University School of Medicine, St. Louis, MO, United States of America.
Matthew A PowellDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, United States of America.
David G MutchDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, United States of America.
Allan B DietzDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States of America.
David T CurielDepartment of Radiation Oncology and Biological Therapeutics Center, Washington University School of Medicine, St. Louis, MO, United States of America.
William G HawkinsAlvin J. Siteman Cancer Center, St. Louis, MO, United States of America.
Dirk SpitzerAlvin J. Siteman Cancer Center, St. Louis, MO, United States of America.ORCID 0000-0003-3949-1815
Washington University in St. Louis · USMayo Clinic in Florida · US

Funding

WU INSTITUTE OF CLINICAL AND TRANSLATIONAL SCIENCESUL1TR002345 · NCATS · WASHINGTON UNIVERSITY · PI William G. Powderly · 2017 to 2026
$97.8M
Washington University Institute of Clinical and Translational SciencesUL1TR000448 · NCATS · WASHINGTON UNIVERSITY · PI EVANOFF, BRADLEY A · 2012 to 2016
$41.4M
NCATS NIH HHS UL1 TR000448NCATS NIH HHS UL1 TR002345NIH HHS UL1 TR000448
6 · The paper itself

Abstract

Clinical application of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-based cancer therapeutics has not reached optimal potencies in part due to inadequate drug stability and inefficiencies in cancer-selective drug delivery. As such, innovative strategies regarding drug design and delivery are of utmost importance to achieve improved treatment results. With our current study, we aimed at exploring the groundwork for a two-stage targeting concept, which is based on the intrinsic tumor homing capacity of mesenchymal stem cells (MSCs) as cellular drug factories for the in situ production of our newly designed and biomarker-targeted TRAIL-based TR3 therapeutics. Since MSCs are primary cells, capable in vitro of only a limited number of cell divisions, identification of suitable strategies for their efficient genetic manipulation is of critical importance. We chose adenoviral (Ad) vectors as a transduction vehicle due to its ability to infect dividing and non-dividing cells and because of their limited restrictions regarding the packaging capacity of their genetic payload. In order to enhance the transduction efficacy of MSCs using Ad5 wild-type-based vectors, we tested a variety of fiber knob modifications on a panel of patient-derived MSC lines established from adipose tissue. We identified Ad5pK7, an Ad5 vector containing a polylysine fiber knob modification, exhibiting the highest transduction rates across a panel of 16 patient-derived MSC lines. We further demonstrated that MSCs could be efficiently transduced with an Ad5pK7 vector containing membrane-anchored and secreted TR3 expression units, including the MUC16 (CA125)-targeted variant Meso64-TR3. In both in vitro and in vivo experiments, MSC-derived Meso64-TR3 was far more potent on MUC16-expressing ovarian cancer compared to its non-targeted TR3 counterpart. Our findings thus provide the foundation to initiate further preclinical investigations on MSC-mediated treatment options in ovarian cancer using biomarker-targeted TR3-based biologics.

Indexed as

Transduction, GeneticAdenoviridaeBiological ProductsFemaleHumansMesenchymal Stem CellsOvarian NeoplasmsTNF-Related Apoptosis-Inducing LigandBiological ProductsTNF-Related Apoptosis-Inducing Ligand

Identifiers

PMID29267342
PMCPMC5739501
OpenAlexW2623020380

What OpenQuestion holds

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LicenceCC BY
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.