Oncolytic vaccinia virus as an adjuvant treatment to cytoreductive surgery for malignant peritoneal mesothelioma

Our plain-English summary of Oncolytic vaccinia virus as an adjuvant treatment to cytoreductive surgery for malignant peritoneal mesothelioma, by S.A. Acuna, K. Ottolino-Perry, B. Çako, et al (Annals of Surgical Oncology, 2014).

The study

• Authors: S.A. Acuna, K. Ottolino-Perry, B. Çako, N. Tang, F.A. Angarita, J.A. McCart
• Journal: Annals of Surgical Oncology
• Published: 2014;21(7):2259-66
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Malignant peritoneal mesothelioma (MPM) is an aggressive cancer with a dismal prognosis. Oncolytic viruses are a promising new therapy for cancer because of their ability to kill tumor cells with minimal toxicity to normal tissues. This experimental study aimed to examine the potential of modified vaccinia virus (VV) to treat MPM when administered alone or as an adjuvant treatment to surgery.

Methods: Two aggressive murine mesothelioma cell lines (AC29, AB12), were used. Cell viability and viral cytopathic effects were assessed using MTS and crystal violet assays. Immunocompetent mice were injected intraperitoneally with MPM cells and treated with intraperitoneal VV. Tumor-bearing mice also underwent cytoreductive surgery (CRS) followed by VV (or control) therapy.

Results: The cytotoxic effects of VV on MPM cell lines was significantly increased compared with the control non-cancer cell line. In both orthotopic models, VV induced tumor regression, prolonging median and long-term survival. VV treatment after incomplete CRS was not superior to VV alone; however, when mice with microscopic disease were treated with VV, further prolongation of median and long-term survivals was observed.

Conclusions: VV selectively kills MPM cells in vitro and leads to improved survival and cures in immunocompetent murine models. Higher efficacy of the virus in the microscopic disease context suggests the use of the virus as an adjuvant treatment to complete surgical resection. These promising results justify further studies of VV in humans as a novel treatment for MPM.

In plain English

This was a laboratory and animal experiment, not a study of people. The authors tested a modified vaccinia virus (vvDD) on two mouse mesothelioma cell lines, AC29 and AB12, made by injecting asbestos (fiber type not named) into mice. In cell culture, the virus killed cancer cells more than normal mouse fibroblasts. At a virus dose (multiplicity of infection) of 1.0, viability 72 hours after infection, relative to uninfected cells, was 32.7 percent for AC29, 61.98 percent for AB12 and 86.45 percent for normal cells. In female mice with abdominal tumors, one virus injection lengthened median survival compared with controls. The gain was 11 days for AC29 (p = 0.088, not statistically significant), with 33.3 percent surviving long-term. It was 9 days for AB12 (p less than 0.001). Giving the virus after partial tumor-removal surgery did no better than virus alone. In AC29 mice treated 3 days after tumor injection, before visible disease, the virus added 10 days of median survival, and 50 percent lived long-term. The authors concluded the virus should be developed further for patients with malignant peritoneal mesothelioma.

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 in mice
• Who was studied: Two mouse mesothelioma cell lines (AC29 and AB12) compared with a normal mouse fibroblast cell line (NIH-3T3), and immunocompetent female CBA/J and BALB/c mice aged 4 to 6 weeks injected in the abdomen with these cancer cells (Toronto, Canada). The number of mice per group is not stated, except n = 4 for the virus distribution test.
• Exposure: The treatment studied was a modified vaccinia virus (vvDD-SR-RFP), given as one injection into the abdomen (1 × 10^9 plaque-forming units), alone or after cytoreductive (tumor-removal) surgery. Asbestos was not the exposure studied: it was only used, earlier, to create the mouse cancer cell lines, and the fiber type is not named.
• Main results:
  • In cell culture at a virus dose (MOI) of 1.0, cell viability measured by MTS assay at 72 hours, relative to mock-infected (uninfected) controls, was 32.7% for AC29, 61.98% for AB12 and 86.45% for the normal NIH-3T3 cells.
  • The virus multiplied more in the two mesothelioma cell lines than in the normal cells, by 2 to 3 logs at 48 hours (p less than 0.05).
  • In AC29 tumor-bearing mice treated 10 days after tumor injection, 33.3% of virus-treated mice were long-term survivors, and median survival rose by 11 days compared with vehicle-treated controls (p = 0.088, not statistically significant).
  • In AB12 tumor-bearing mice, the virus improved median survival by 9 days compared with vehicle-treated controls (p less than 0.001).
  • No signs of toxicity caused by the virus were seen in the treated mice.
  • Seventy-two hours after injection, virus was found mainly in tumor tissue. Levels were tenfold lower in the ovaries and lower or undetectable in other tissues.
  • Surgery reduced tumor burden by 53.8% (AC29) and 60% (AB12), but disease was left behind on the small bowel and other critical organs.
  • Virus alone and surgery alone each improved survival compared with sham surgery plus vehicle (p less than 0.05). Virus combined with surgery was not better than virus alone.
  • In AC29 tumor-bearing mice only, treated 3 days after tumor injection when no disease was visible, the virus increased median survival by 10 days (p = 0.001), and 50% of mice lived long-term.
• The authors' conclusion: The authors concluded that the virus showed significant activity against mesothelioma cells, improved survival in the mouse models, and should be further developed for clinical use in patients with malignant peritoneal mesothelioma.
• Limitations the authors state:
  • Because the mouse model is technically difficult, the surgery could remove only part of the visible tumors.
  • Complete surgery was not actually tested. Early treatment of microscopic disease was used as a stand-in for complete surgical removal.
  • The authors note there is room to improve on the results.

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: Cytoreductive Surgery, Peritoneal Mesothelioma, Prognosis, Mesothelioma, Surgical Resection.

Related studies

• Regional delivery of oncolytic vaccinia virus: it's time for clinical trials — S. Downs-Canner, D.L. Bartlett (2014)
• Adjuvant dendritic cell based immunotherapy (DCBI) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal mesothelioma, a phase II single centre open-label clinical trial: rationale and design of the MESOPEC trial — N.L. de Boer, J.P. van Kooten, et al. (2019)
• The Role of Ki-67 and Pre-cytoreduction Parameters in Selecting Diffuse Malignant Peritoneal Mesothelioma (DMPM) Patients for Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) — S. Kusamura, P.A. Torres Mesa, et al. (2016)
• The role of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal carcinomatosis: a systematic review including evidence from Japan — T. Kitai (2021)
• Cytokine-armed vaccinia virus infects the mesothelioma tumor microenvironment to overcome immune tolerance and mediate tumor resolution — C. Jackaman, D.J. Nelson (2010)
• Institutional learning curve of cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion for peritoneal malignancies — P.M. Polanco, Y. Ding, et al. (2015)

Browse more research in Annals of Surgical Oncology, or return to medical research.