Regional delivery of oncolytic vaccinia virus: it's time for clinical trials

Our plain-English summary of Regional delivery of oncolytic vaccinia virus: it's time for clinical trials, by S. Downs-Canner, D.L. Bartlett (Annals of Surgical Oncology, 2014).

The study

• Authors: S. Downs-Canner, D.L. Bartlett
• Journal: Annals of Surgical Oncology
• Published: 2014;21(7):2127-8
• Type of article: Editorial, Comment
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

In plain English

This article was an editorial, not an original study. The authors commented on a mouse study by Acuna et al., published in the same journal issue. That study tested a modified virus called double-deleted vaccinia virus (vvDD), delivered directly into the abdominal cavity, as a treatment for malignant peritoneal mesothelioma. The editorial did not discuss asbestos. As the editorial describes it, Acuna et al. found that vvDD killed cells from two mesothelioma cell lines, improved survival in two mouse models of peritoneal mesothelioma, and multiplied only in the tumor and the ovary. Among mice with only microscopic disease, fifty percent were cured after a single injection of 1 × 10^9 (one billion) plaque-forming units of vvDD. The editorial authors noted limits. There was no suitable animal model for cytoreductive surgery, and the microscopic-disease model was imperfect. The timing, spread and safety of giving the virus after surgery had not been addressed. They wrote that no human trials in mesothelioma had been reported, though they knew of three ongoing Phase I trials in pleural mesothelioma. The authors concluded that the results should be confirmed in a clinical trial.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Editorial commenting on another study (Acuna et al.) published in the same journal issue; not original research
• Who was studied: No population of its own. The editorial discusses a mouse (murine) model of peritoneal mesothelioma studied by Acuna et al., plus two mesothelioma cell lines
• Exposure: No asbestos exposure is discussed. The treatment discussed is double-deleted oncolytic vaccinia virus (vvDD), given regionally into the peritoneal cavity
• Main results:
  • Acuna et al. (as reported by the editorial) showed that vvDD selectively killed cells from two different mesothelioma cell lines
  • Acuna et al. (as reported by the editorial) found improved survival in two different orthotopic mouse models of malignant peritoneal mesothelioma after intraperitoneal vvDD
  • Acuna et al. (as reported by the editorial) found that the virus replicated only in the tumor and the ovary
  • In Acuna et al.'s model of microscopic disease, mice treated with vvDD had a significant survival benefit compared with controls. Fifty percent of the mice were cured after a single intraperitoneal injection of 1 × 10^9 plaque-forming units of vvDD (printed in the scanned text as '1 9 109')
  • The editorial authors stated that no human trials of these viruses in mesothelioma had been reported, but that they knew of three ongoing Phase I trials using oncolytic vaccinia, measles or herpes virus for pleural mesothelioma
• The authors' conclusion: The authors concluded that Acuna et al.'s results should be confirmed in a clinical trial, where vvDD may provide a survival benefit to patients
• Limitations the authors state:
  • There was no suitable animal model for cytoreductive surgery, so it is hard to conclude that surgery combined with vvDD improves survival over either treatment alone
  • The 'microscopic disease' model is imperfect because it represents an early tumor environment rather than a mature one that has been treated surgically
  • The best timing of virus delivery after cytoreduction, and whether surgical scarring prevents the virus from spreading in the peritoneal cavity, had not been addressed
  • The complexity and safety of giving a live virus right after surgery still need to be addressed

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma, Peritoneal mesothelioma.

Medical terms in this study, explained in our Lexicon: Clinical Trial.

Related studies

• Oncolytic vaccinia virus as an adjuvant treatment to cytoreductive surgery for malignant peritoneal mesothelioma — S.A. Acuna, K. Ottolino-Perry, et al. (2014)
• Clinical Trials with Oncolytic Measles Virus: Current Status and Future Prospects — P. Msaouel, M. Opyrchal, et al. (2018)
• Cytokine-armed vaccinia virus infects the mesothelioma tumor microenvironment to overcome immune tolerance and mediate tumor resolution — C. Jackaman, D.J. Nelson (2010)
• Frequent Homozygous Deletions of Type I Interferon Genes in Pleural Mesothelioma Confer Sensitivity to Oncolytic Measles Virus — T. Delaunay, C. Achard, et al. (2020)
• Genetically engineered oncolytic Newcastle disease virus effectively induces sustained remission of malignant pleural mesothelioma — G.R. Silberhumer, P. Brader, et al. (2010)
• Personalized Oncolytic Therapy: The Next Step Toward the Successful Clinical Application of Vaccine-Strain Measles Viruses for Cancer Therapy? — T. Peikert (2020)

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