Evidence map›Paper›PMID 28387831›Full record

ArticleNeuro-oncology2017

Retroviral replicating vector-mediated gene therapy achieves long-term control of tumor recurrence and leads to durable anticancer immunity.

Kei Hiraoka, Akihito Inagaki, Yuki Kato, Tiffany T Huang, Leah A Mitchell, Shuichi Kamijima, Masamichi Takahashi, Hiroshi Matsumoto, Katrin Hacke, Carol A Kruse and 5 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuro-oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
6.2field-weighted citation impact, top 4% 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

35 citing papers in PubMed, 50 citations in OpenAlex.

  1. Trial
  2. Article
  3. Designing nucleic acid-based therapeutics for cancer treatment: Updates on the state of the art.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Review
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  14. Prodrugs and prodrug-activated systems in gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2021
    Review
  15. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 3 institutions in 1 country.

Kei HiraokaDepartment of Medicine, University of California Los Angeles (UCLA), Los Angeles, California; Department of Cell Biology and Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida; Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California; Tocagen Inc., San Diego, California; Department of Neurosurgery, University of California Los Angeles, Los Angeles, California.
Akihito InagakiDepartment of Medicine, University of California Los Angeles (UCLA), Los Angeles, California; Department of Cell Biology and Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida; Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California; Tocagen Inc., San Diego, California; Department of Neurosurgery, University of California Los Angeles, Los Angeles, California.
Yuki KatoDepartment of Medicine, University of California Los Angeles (UCLA), Los Angeles, California; Department of Cell Biology and Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida; Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California; Tocagen Inc., San Diego, California; Department of Neurosurgery, University of California Los Angeles, Los Angeles, California.
Tiffany T HuangDepartment of Medicine, University of California Los Angeles (UCLA), Los Angeles, California; Department of Cell Biology and Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida; Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California; Tocagen Inc., San Diego, California; Department of Neurosurgery, University of California Los Angeles, Los Angeles, California.
Leah A MitchellDepartment of Medicine, University of California Los Angeles (UCLA), Los Angeles, California; Department of Cell Biology and Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida; Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California; Tocagen Inc., San Diego, California; Department of Neurosurgery, University of California Los Angeles, Los Angeles, California.
Shuichi KamijimaDepartment of Medicine, University of California Los Angeles (UCLA), Los Angeles, California; Department of Cell Biology and Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida; Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California; Tocagen Inc., San Diego, California; Department of Neurosurgery, University of California Los Angeles, Los Angeles, California.
Masamichi TakahashiDepartment of Medicine, University of California Los Angeles (UCLA), Los Angeles, California; Department of Cell Biology and Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida; Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California; Tocagen Inc., San Diego, California; Department of Neurosurgery, University of California Los Angeles, Los Angeles, California.
Hiroshi MatsumotoDepartment of Medicine, University of California Los Angeles (UCLA), Los Angeles, California; Department of Cell Biology and Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida; Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California; Tocagen Inc., San Diego, California; Department of Neurosurgery, University of California Los Angeles, Los Angeles, California.
Katrin HackeDepartment of Medicine, University of California Los Angeles (UCLA), Los Angeles, California; Department of Cell Biology and Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida; Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California; Tocagen Inc., San Diego, California; Department of Neurosurgery, University of California Los Angeles, Los Angeles, California.
Carol A KruseDepartment of Medicine, University of California Los Angeles (UCLA), Los Angeles, California; Department of Cell Biology and Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida; Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California; Tocagen Inc., San Diego, California; Department of Neurosurgery, University of California Los Angeles, Los Angeles, California.
Derek OstertagDepartment of Medicine, University of California Los Angeles (UCLA), Los Angeles, California; Department of Cell Biology and Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida; Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California; Tocagen Inc., San Diego, California; Department of Neurosurgery, University of California Los Angeles, Los Angeles, California.
Joan M RobbinsDepartment of Medicine, University of California Los Angeles (UCLA), Los Angeles, California; Department of Cell Biology and Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida; Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California; Tocagen Inc., San Diego, California; Department of Neurosurgery, University of California Los Angeles, Los Angeles, California.
Harry E GruberDepartment of Medicine, University of California Los Angeles (UCLA), Los Angeles, California; Department of Cell Biology and Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida; Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California; Tocagen Inc., San Diego, California; Department of Neurosurgery, University of California Los Angeles, Los Angeles, California.
Douglas J JollyDepartment of Medicine, University of California Los Angeles (UCLA), Los Angeles, California; Department of Cell Biology and Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida; Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California; Tocagen Inc., San Diego, California; Department of Neurosurgery, University of California Los Angeles, Los Angeles, California.
Noriyuki KasaharaDepartment of Medicine, University of California Los Angeles (UCLA), Los Angeles, California; Department of Cell Biology and Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida; Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California; Tocagen Inc., San Diego, California; Department of Neurosurgery, University of California Los Angeles, Los Angeles, California.
University of Miami · USSylvester Comprehensive Cancer Center · USUniversity of California, Los Angeles · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundProdrug-activator gene therapy with Toca 511, a tumor-selective retroviral replicating vector (RRV) encoding yeast cytosine deaminase, is being evaluated in recurrent high-grade glioma patients. Nonlytic retroviral infection leads to permanent integration of RRV into the cancer cell genome, converting infected cancer cell and progeny into stable vector producer cells, enabling ongoing transduction and viral persistence within tumors. Cytosine deaminase in infected tumor cells converts the antifungal prodrug 5-fluorocytosine into the anticancer drug 5-fluorouracil, mediating local tumor destruction without significant systemic adverse effects.

methodsHere we investigated mechanisms underlying the therapeutic efficacy of this approach in orthotopic brain tumor models, employing both human glioma xenografts in immunodeficient hosts and syngeneic murine gliomas in immunocompetent hosts.

resultsIn both models, a single injection of replicating vector followed by prodrug administration achieved long-term survival benefit. In the immunodeficient model, tumors recurred repeatedly, but bioluminescence imaging of tumors enabled tailored scheduling of multicycle prodrug administration, continued control of disease burden, and long-term survival. In the immunocompetent model, complete loss of tumor signal was observed after only 1-2 cycles of prodrug, followed by long-term survival without recurrence for >300 days despite discontinuation of prodrug. Long-term survivors rejected challenge with uninfected glioma cells, indicating immunological responses against native tumor antigens, and immune cell depletion showed a critical role for CD4+ T cells.

conclusionThese results support dual mechanisms of action contributing to the efficacy of RRV-mediated prodrug-activator gene therapy: long-term tumor control by prodrug conversion-mediated cytoreduction, and induction of antitumor immunity.

Indexed as

AnimalsBrain NeoplasmsCell Line, TumorCell SurvivalCytosine DeaminaseFemaleGenetic TherapyGenetic VectorsGliomaHumansMiceNeoplasm Recurrence, LocalRetroviridaeSurvival AnalysisCytosine Deaminaseantitumor immunityprodrug activator gene therapyretroviral replicating vectorToca 511

Identifiers

PMID28387831
PMCPMC5574670
OpenAlexW2604496912

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

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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.