Genetically engineered oncolytic Newcastle disease virus effectively induces sustained remission of malignant pleural mesothelioma

Our plain-English summary of Genetically engineered oncolytic Newcastle disease virus effectively induces sustained remission of malignant pleural mesothelioma, by G.R. Silberhumer, P. Brader, J. Wong, et al (Molecular Cancer Therapeutics, 2010).

The study

• Authors: G.R. Silberhumer, P. Brader, J. Wong, I.S. Serganova, M. Gönen, S.J. Gonzalez, R. Blasberg, D. Zamarin, Y. Fong
• Journal: Molecular Cancer Therapeutics
• Published: 2010;9(10):2761-9
• Cited by: 33 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma is a highly aggressive tumor. Alternative treatment strategies such as oncolytic viral therapy may offer promising treatment options in the future. In this study, the oncolytic efficacy and induction of tumor remission by a genetically engineered Newcastle disease virus [NDV; NDV(F3aa)-GFP; GFP, green fluorescent protein] in malignant pleural mesothelioma is tested and monitored by bioluminescent tumor imaging. The efficacy of NDV(F3aa)-GFP was tested against several mesothelioma cell lines in vitro. Firefly luciferase-transduced MSTO-211H* orthotopic pleural mesothelioma tumor-bearing animals were treated with either single or multiple doses of NDV(F3aa)-GFP at different time points (days 1 and 10) after tumor implantation. Tumor burden was assessed by bioluminescence imaging. Mesothelioma cell lines exhibited dose-dependent susceptibility to NDV lysis in the following order of sensitivity: MSTO-211H > MSTO-211H* > H-2452 > VAMT > JMN. In vivo studies with MSTO-211H* cells showed complete response to viral therapy in 65% of the animals within 14 days after treatment initiation. Long-term survival in all of these animals was >50 days after tumor installation (control animals, <23 d). Multiple treatment compared with single treatment showed a significantly better response (P = 0.005). NDV seems to be an efficient viral oncolytic agent in the therapy of malignant pleural mesothelioma in an orthotopic pleural mesothelioma tumor model.

In plain English

This laboratory and mouse study, from Memorial Sloan-Kettering Cancer Center, tested a genetically engineered Newcastle disease virus, NDV(F3aa)-GFP, as a treatment for malignant pleural mesothelioma. It did not study asbestos exposure. In the dish, the virus killed human mesothelioma cells: at the higher dose tested, cell kill by day 7 was 88% to 97% in four cell lines. In mice, the authors implanted human mesothelioma cells (MSTO-211H, altered to glow for imaging) in the chest lining. They then injected the virus into the chest either once or four times, starting 1 or 10 days after implantation, in groups of five mice. Ten control mice received salt solution, and all of them were sacrificed within 24 days because of tumor. In early-treated mice, the tumor signal vanished in 4 of 5 given one dose and in all 5 given multiple doses. Multiple doses gave better survival than one dose (P = 0.005). Survival did not differ significantly between day-1 and day-10 starts (P = 0.84). No signs of viral toxicity were seen. The authors concluded that the virus showed promising results and called for further investigation.

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: Laboratory (cell culture) and animal experiment testing an engineered virus as a cancer treatment
• Who was studied: Human mesothelioma cell lines. Female athymic mice with implanted human MSTO-211H mesothelioma cells, in four treatment groups of five mice each and a control group of 10 mice. The work was done at Memorial Sloan-Kettering Cancer Center; study dates are not given.
• Exposure: No asbestos exposure was studied; asbestos is mentioned only in the introduction as a cause of the disease. The treatment studied was genetically engineered Newcastle disease virus NDV(F3aa)-GFP, injected into the chest cavity of mice. It was given as one dose or as four doses every other day, starting 1 or 10 days after tumor implantation.
• Main results:
  • In cell culture, by day 7, cell kill at the two higher virus doses (MOI 0.1 and 1) was 67%/88% for JMN, 77%/93% for H-2452, 90%/93% for MSTO-211H and 91%/97% for VAMT.
  • All 10 control mice, which received salt solution (PBS) instead of virus, were sacrificed within 24 days because of disease burden.
  • Single dose on day 1 (5 mice): 3 of 5 survived the entire 4-month follow-up without a tumor signal.
  • Multiple doses starting day 1 (5 mice): the tumor signal disappeared in all animals within 12 days.
  • Across groups, multiple doses gave significantly better survival than a single dose (P = 0.005).
  • Survival did not differ significantly between mice whose treatment started on day 1 and mice whose treatment started on day 10 (P = 0.84).
  • No signs of viral toxicity were observed in the treated mice.
• The authors' conclusion: The authors concluded that NDV showed promising results against malignant pleural mesothelioma and that the findings call for further investigation.
• Limitations the authors state:
  • The authors stated that the reasons why different cell lines respond differently to the virus are speculative and need further study.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Mesothelioma, Tumor Burden.

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