Evidence map›Paper›PMID 21772252›Full record

Trial reportMolecular therapy : the journal of the American Society of Gene Therapy2011

A mechanistic proof-of-concept clinical trial with JX-594, a targeted multi-mechanistic oncolytic poxvirus, in patients with metastatic melanoma.

Tae-Ho Hwang, Anne Moon, James Burke, Antoni Ribas, Joe Stephenson, Caroline J Breitbach, Manijeh Daneshmand, Naomi De Silva, Kelley Parato, Jean-Simon Diallo and 4 more

Open access · hybridAbstract readClinical Trial
In one paragraph

Trial report in Molecular therapy : the journal of the American Society of Gene Therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
91citing papers in PubMed, 3 pooled it
8.6field-weighted citation impact, top 2% 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

91 citing papers in PubMed, 3 syntheses or guidelines pooled it, 158 citations in OpenAlex.

  1. Pooled it
  2. Clinical Application of Oncolytic Viruses: A Systematic Review.International journal of molecular sciences · 2020
    Pooled it
  3. Pooled it
  4. Trial
  5. Trial
  6. The role and mechanism of neutrophils in oncolytic virus therapy.Experimental biology and medicine (Maywood, N.J.) · 2026
    Review
  7. Review
  8. Review
  9. Review
  10. Review
  11. Virus nanotechnology for intratumoural immunotherapy.Nature reviews bioengineering · 2024
    Article
  12. Article
  13. Exploring treatment options in cancer: Tumor treatment strategies.Signal transduction and targeted therapy · 2024
    Review
  14. Article
  15. Review
  16. Review
  17. Review
  18. Vaccinating against cancer: getting to prime time.Journal for immunotherapy of cancer · 2023
    Review
  19. Article
  20. Review

31 more citing papers are in PubMed but not listed here.

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 6 institutions in 3 countries.

Tae-Ho HwangDepartment of Clinical Pharmacology, Pusan National University, Busan, South Korea. thhwang@pusan.ac.kr
Anne Moon
James Burke
Antoni Ribas
Joe Stephenson
Caroline J Breitbach
Manijeh Daneshmand
Naomi De Silva
Kelley Parato
Jean-Simon Diallo
Yeon-Sook Lee
Ta-Chiang Liu
John C Bell
David H Kirn
University of Ottawa · CAOttawa Hospital · CAPusan National University · KRBillings Clinic · USSouth Carolina Oncology Associates · USUCLA Medical Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

JX-594 is a targeted and granulocyte macrophage-colony stimulating factor (GM-CSF)-expressing oncolytic poxvirus designed to selectively replicate in and destroy cancer cells through viral oncolysis and tumor-specific immunity. In order to study the mechanisms-of-action (MOA) of JX-594 in humans, a mechanistic proof-of-concept clinical trial was performed at a low dose equivalent to ≤10% of the maximum-tolerated dose (MTD) in other clinical trials. Ten patients with previously treated stage IV melanoma were enrolled. Tumors were injected weekly for up to nine total treatments. Blood samples and tumor biopsies were analyzed for evidence of transgene activity, virus replication, and immune stimulation. The β-galactosidase (β-gal) transgene was expressed in all patients as evidenced by antibody induction. Six patients had significant induction of GM-CSF-responsive white blood cell (WBC) subsets such as neutrophils (25-300% increase). JX-594 replication and subsequent shedding into blood was detectable in five patients after cycles 1-9. Tumor biopsies demonstrated JX-594 replication, perivascular lymphocytic infiltration, and diffuse tumor necrosis. Mild flu-like symptoms were the most common adverse events. In sum, JX-594 replication, oncolysis, and expression of both transgenes were demonstrated; replication was still evident after multiple cycles. These findings have implications for further clinical development of JX-594 and other transgene-armed oncolytic viruses.

Indexed as

Oncolytic VirotherapyAdultAgedFemaleGranulocyte-Macrophage Colony-Stimulating FactorHumansMaleMelanomaMiddle AgedNeoplasm MetastasisPoxviridaeTransgenesGranulocyte-Macrophage Colony-Stimulating Factor

Identifiers

PMID21772252
PMCPMC3188739
OpenAlexW1978558644

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.