Evidence map›Paper›PMID 26359629›Full record

ArticleOncotarget2015

Rigorous optimization and validation of potent RNA CAR T cell therapy for the treatment of common epithelial cancers expressing folate receptor.

Keith Schutsky, D Gang Song, Rachel Lynn, Jenessa B Smith, Mathilde Poussin, Mariangela Figini, Yangbing Zhao, Daniel J Powell

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.6field-weighted citation impact, top 9% 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

29 citing papers in PubMed, 51 citations in OpenAlex.

  1. Advances inMolecular therapy. Nucleic acids · 2026
    Review
  2. Article
  3. Article
  4. Folate Receptor Alpha-A Secret Weapon in Ovarian Cancer Treatment?International journal of molecular sciences · 2024
    Review
  5. Review
  6. Review
  7. RNA-Based Therapeutic Technology.International journal of molecular sciences · 2023
    Review
  8. Review
  9. Review
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Review
  16. Review
  17. RNA-Modified T Cells Mediate Effective Delivery of Immunomodulatory Cytokines to Brain Tumors.Molecular therapy : the journal of the American Society of Gene Therapy · 2019
    Article
  18. The Emerging Role of In Vitro-Transcribed mRNA in Adoptive T Cell Immunotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2019
    Review
  19. 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 at 3 institutions in 2 countries.

Keith SchutskyOvarian Cancer Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
D Gang SongOvarian Cancer Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Rachel LynnOvarian Cancer Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Jenessa B SmithOvarian Cancer Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Mathilde PoussinOvarian Cancer Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Mariangela FiginiDepartment of Experimental Oncology and Molecular Medicine, Istituto Nazionale dei Tumori, 20133, Milan, Italy.
Yangbing ZhaoOvarian Cancer Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Daniel J PowellOvarian Cancer Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Cancer Research Center · USUniversity of Pennsylvania · USFondazione IRCCS Istituto Nazionale dei Tumori · IT

Funding

PREDOCTORAL TRAINING PROGRAM IN PHARMACOLOGYT32GM008076 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI BLENDY, JULIE A · 1985 to 2023
$10.8M
A Universal Approach to Personalized Adoptive T cell Therapy of CancerR01CA168900 · NCI · UNIVERSITY OF PENNSYLVANIA · PI POWELL, DANIEL J. · 2012 to 2016
$1.6M
NCI NIH HHS R01 CA168900NCI NIH HHS R01-CA168900NIGMS NIH HHS T32 GM008076
6 · The paper itself

Abstract

Using lentiviral technology, we recently demonstrated that incorporation of CD27 costimulation into CARs greatly improves antitumor activity and T cell persistence. Still, virus-mediated gene transfer is expensive, laborious and enables long-term persistence, creating therapies which cannot be easily discontinued if toxic. To address these concerns, we utilized a non-integrating RNA platform to engineer human T cells to express FRα-specific, CD27 CARs and tested their capacity to eliminate human FRα(+) cancer. Novel CARs comprised of human components were constructed, C4-27z and C4opt-27z, a codon-optimized variant created for efficient expression. Following RNA electroporation, C4-27z and C4opt-27z CAR expression is initially ubiquitous but progressively declines across T cell populations. In addition, C4-27z and C4opt-27z RNA CAR T cells secrete high levels of Th-1 cytokines and display strong cytolytic function against human FRα(+) cancers in a time- and antigen-dependent manner. Further, C4-27z and C4opt-27z CAR T cells exhibit significant proliferation in vivo, facilitate the complete regression of fully disseminated human ovarian cancer xenografts in mice and reduce the progression of solid ovarian cancer. These results advocate for rapid progression of C4opt-27z RNA CAR to the clinic and establish a new paradigm for preclinical optimization and validation of RNA CAR candidates destined for clinical translation.

Indexed as

AnimalsCarcinoma, Ovarian EpithelialCell Line, TumorCell ProliferationCombined Modality TherapyCytokinesCytotoxicity, ImmunologicElectroporationFemaleFolate Receptor 1Gene Expression RegulationGenetic TherapyHumansImmunotherapy, AdoptiveLymphocytes, Tumor-InfiltratingMice, Inbred NODCytokinesFolate Receptor 1FOLR1 protein, humanRNASingle-Chain AntibodiesTumor Necrosis Factor Receptor Superfamily, Member 7adoptive immunotherapychimeric antigen receptorfolate receptor alphaovarian cancerT cells

Identifiers

PMID26359629
PMCPMC4745700
OpenAlexW2113888845

What OpenQuestion holds

Textmetadata
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.