Evidence map›Paper›PMID 25301172›Full record

ArticleCancer gene therapy2014

Radiosensitization of gliomas by intracellular generation of 5-fluorouracil potentiates prodrug activator gene therapy with a retroviral replicating vector.

Masamichi Takahashi, Gilmer Valdes, Kei Hiraoka, Akihito Inagaki, Shuichi Kamijima, Ewa Micewicz, Harry E Gruber, Joan M Robbins, Douglas J Jolly, William H McBride and 2 more

3 registry-linked trialsOpen access · bronzeAbstract read
In one paragraph

Article in Cancer gene therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
1.4field-weighted citation impact, top 18% 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.

NCT01156584 phase1completednot on this map

A Phase 1 Ascending Dose Trial of the Safety and Tolerability of Toca 511 in Patients With Recurrent High Grade Glioma

TypeinterventionalSponsorTocagen Inc.Ran2010 to 2016Enrolled54ConditionsGlioblastoma, Anaplastic Astrocytoma, Anaplastic Oligodendroglioma, Anaplastic OligoastrocytomaArmsToca 511 vector, Toca FC
NCT01470794 phase1completednot on this map

A Phase 1 Ascending Dose Trial of Safety and Tolerability of Toca 511, a Retroviral Replicating Vector, Administered to Subjects at the Time of Resection for Recurrent High Grade Glioma & Followed by Treatment With Toca FC, Extended-Release 5-FC

TypeinterventionalSponsorTocagen Inc.Ran2012 to 2016Enrolled58ConditionsGlioblastoma Multiforme, Anaplastic Astrocytoma, Anaplastic Oligodendroglioma, Anaplastic OligoastrocytomaArmsToca 511 vector, Toca FC
NCT01985256 phase1completednot on this map

A Phase 1 Ascending Dose Trial of the Safety and Tolerability of Toca 511, a Retroviral Replicating Vector, Administered Intravenously Prior to, and Intracranially at the Time of, Subsequent Resection for Recurrent HGG & Followed by Treatment With Extended-Release 5-FC

TypeinterventionalSponsorTocagen Inc.Ran2014 to 2016Enrolled17ConditionsGlioblastoma Multiforme, Anaplastic Astrocytoma, Anaplastic Oligodendroglioma, Anaplastic OligoastrocytomaArmsToca 511, Toca FC
3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 39 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Cell and gene therapy in neuro-oncology.Handbook of clinical neurology · 2024
    Review
  5. Article
  6. Gene Therapy for High Grade Glioma: The Clinical Experience.Expert opinion on biological therapy · 2023
    Review
  7. Article
  8. Radiosensitization to γ-Ray by Functional Inhibition of APOBEC3G.International journal of molecular sciences · 2022
    Article
  9. Review
  10. Review
  11. Review
  12. Review
  13. Current Approaches for Glioma Gene Therapy and Virotherapy.Frontiers in molecular neuroscience · 2021
    Review
  14. Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Review
  20. Review
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

12 authors at 2 institutions in 1 country.

Masamichi Takahashi *Department of Medicine, University of California Los Angeles (UCLA), Los Angeles, California, USA.
Gilmer Valdes *Department of Radiation Oncology, University of California Los Angeles (UCLA), Los Angeles, California, USA.
Kei HiraokaDepartment of Medicine, University of California Los Angeles (UCLA), Los Angeles, California, USA.
Akihito InagakiDepartment of Medicine, University of California Los Angeles (UCLA), Los Angeles, California, USA.
Shuichi KamijimaDepartment of Medicine, University of California Los Angeles (UCLA), Los Angeles, California, USA.
Ewa MicewiczDepartment of Radiation Oncology, University of California Los Angeles (UCLA), Los Angeles, California, USA.
Harry E GruberTocagen Inc., San Diego, California, USA.
Joan M RobbinsTocagen Inc., San Diego, California, USA.
Douglas J JollyTocagen Inc., San Diego, California, USA.
William H McBrideDepartment of Radiation Oncology, University of California Los Angeles (UCLA), Los Angeles, California, USA.
Keisuke S IwamotoDepartment of Radiation Oncology, University of California Los Angeles (UCLA), Los Angeles, California, USA.
Noriyuki KasaharaDepartment of Medicine, University of California Los Angeles (UCLA), Los Angeles, California, USA.
University of California, Los Angeles · USRetriev Technologies (United States) · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
Pilot and Feasibility ProgramP30DK041301 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ROZENGURT, JUAN ENRIQUE · 1990 to 2019
$18.0M
Translational Development of Replication-Competent Retrovirus VectorsU01NS059821 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KASAHARA, NORIYUKI · 2010 to 2013
$2.9M
NCI NIH HHS P30 CA016042NIDDK NIH HHS P30 DK041301NINDS NIH HHS U01 NS059821
6 · The paper itself

Abstract

A tumor-selective non-lytic retroviral replicating vector (RRV), Toca 511, and an extended-release formulation of 5-fluorocytosine (5-FC), Toca FC, are currently being evaluated in clinical trials in patients with recurrent high-grade glioma (NCT01156584, NCT01470794 and NCT01985256). Tumor-selective propagation of this RRV enables highly efficient transduction of glioma cells with cytosine deaminase (CD), which serves as a prodrug activator for conversion of the anti-fungal prodrug 5-FC to the anti-cancer drug 5-fluorouracil (5-FU) directly within the infected cells. We investigated whether, in addition to its direct cytotoxic effects, 5-FU generated intracellularly by RRV-mediated CD/5-FC prodrug activator gene therapy could also act as a radiosensitizing agent. Efficient transduction by RRV and expression of CD were confirmed in the highly aggressive, radioresistant human glioblastoma cell line U87EGFRvIII and its parental cell line U87MG (U87). RRV-transduced cells showed significant radiosensitization even after transient exposure to 5-FC. This was confirmed both in vitro by a clonogenic colony survival assay and in vivo by bioluminescence imaging analysis. These results provide a convincing rationale for development of tumor-targeted radiosensitization strategies utilizing the tumor-selective replicative capability of RRV, and incorporation of radiation therapy into future clinical trials evaluating Toca 511 and Toca FC in brain tumor patients.

Indexed as

AnimalsCell Line, TumorCell SurvivalCytosine DeaminaseDisease Models, AnimalDose-Response Relationship, RadiationFemaleFluorouracilGene ExpressionGene OrderGenes, ReporterGenes, Transgenic, SuicideGenetic TherapyGenetic VectorsGene Transfer TechniquesGliomaCytosine DeaminaseFluorouracilProdrugs

Identifiers

PMID25301172
PMCPMC4246057
OpenAlexW1992780905

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

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.