Efficacy of Different Oncolytic Vaccinia Virus Strains for the Treatment of Murine Peritoneal Mesothelioma

Our plain-English summary of Efficacy of Different Oncolytic Vaccinia Virus Strains for the Treatment of Murine Peritoneal Mesothelioma, by C. Yurttas, J. Beil, S. Berchtold, et al (Cancers, 2024).

The study

• Authors: C. Yurttas, J. Beil, S. Berchtold, I. Smirnow, L.D. Kloker, B. Sipos, M.W. Löffler, A. Königsrainer, A.L. Mihaljevic, U.M. Lauer, K. Thiel
• Journal: Cancers
• Published: 2024;16(2)
• Read it: PubMed · Publisher · Free full text

Abstract

Effective treatment options for peritoneal surface malignancies (PSMs) are scarce. Oncolytic virotherapy with recombinant vaccinia viruses might constitute a novel treatment option for PSM. We aimed to identify the most effective oncolytic vaccinia virus strain in two murine mesothelioma cell lines and the oncolytic potential in a murine model of peritoneal mesothelioma. Cell lines AB12 and AC29 were infected in vitro with vaccinia virus strains Lister (GLV-1h254), Western Reserve (GLV-0b347), and Copenhagen (GLV-4h463). The virus strain GLV-0b347 was shown most effective in vitro and was further investigated by intraperitoneal (i.p.) application to AB12 and AC29 mesothelioma-bearing mice. Feasibility, safety, and effectiveness of virotherapy were assessed by evaluating the peritoneal cancer index (PCI), virus detection in tumor tissues and ascites, virus growth curves, and comparison of overall survival. After i.p. injection of GLV-0b347, virus was detected in both tumor cells and ascites. In comparison to mock-treated mice, overall survival was significantly prolonged, ascites was less frequent and PCI values declined. However, effective treatment was only observed in animals with limited tumor burden at the time point of virus application. Nonetheless, intraperitoneal virotherapy with GLV-0b347 might constitute a novel therapeutic option for the treatment of peritoneal mesothelioma. Additional treatment modifications and combinational regimes will be investigated to further enhance treatment efficacy.

In plain English

This laboratory study compared three oncolytic vaccinia virus strains in murine peritoneal mesothelioma. The cell lines AB12 and AC29, generated by intraperitoneal asbestos injection into BALB/c and CBA/j mice, were infected in vitro with GLV-1h254 (Lister), GLV-0b347 (Western Reserve) and GLV-4h463 (Copenhagen). GLV-0b347 killed the most cells (in AB12, about 60% at MOI 0.1 and 90% at MOI 1, versus 0% to 20% for the other strains) and reached the highest titres. GLV-0b347 (5 x 10(6) pfu) was then given intraperitoneally to tumour-bearing mice. Infectious virus was recovered from tumours of three of five AB12-bearing and two of five AC29-bearing mice. Given 10 days after implantation of larger cell numbers, virus did not significantly improve survival (p = 0.2322, p = 0.2589). With fewer tumour cells and treatment at day 5, the authors reported significantly prolonged survival in both models, although the printed p values (0.094 for CBA/j, 0.0004 for BALB/c) do not both meet the stated threshold of p below 0.05. Peritoneal cancer index values fell, and ascites occurred in 20% of virus-treated versus 100% of mock-treated AC29 mice.

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 study: in vitro infection of two murine mesothelioma cell lines plus in vivo experiments in syngeneic mouse models
• Who was studied: Murine peritoneal mesothelioma cell lines AB12 and AC29 (both originally induced by intraperitoneal asbestos injection), and female BALB/c and CBA/j mice bearing orthotopic peritoneal mesothelioma; work carried out in Tübingen, Germany, animal protocol approved July 2021
• Exposure: Oncolytic vaccinia virus strains GLV-1h254 (Lister), GLV-0b347 (Western Reserve) and GLV-4h463 (Copenhagen) at MOI 0.0001 to 1 in vitro; GLV-0b347 5 x 10(6) pfu given intraperitoneally in vivo
• Main results:
  • In AB12 cells at 96 hours post infection, GLV-1h254 and GLV-4h463 caused 0% to a maximum of 20% cell death at MOI 0.1 or 1, while GLV-0b347 caused about 60% at MOI 0.1 and up to 90% at MOI 1
  • In AC29 cells, GLV-4h463 reduced cells by 30% at MOI 1 and GLV-1h254 by about 50%, while GLV-0b347 reduced cells by 80% at MOI 0.1 and by more than 90% at MOI 1
  • GLV-0b347 reached its highest titres at 48 hours post infection, above 1 x 10(7) pfu/mL at MOI 1 and above 1 x 10(6) pfu/mL at MOI 0.1, exceeding the other two constructs in both cell lines
  • After intraperitoneal injection, infectious virus was found in tumours of 3 of 5 AB12-bearing mice (60%) and 2 of 5 AC29-bearing mice (40%)
  • In the first in vivo setup (higher cell numbers, virus at day 10), virus-treated AB12-bearing mice lived on average one day longer and AC29-bearing mice half a day longer, with no statistically significant survival difference (p = 0.2322 and p = 0.2589)
  • With reduced tumour cell numbers and virus given on day 5, the authors described survival of virus-treated CBA/j and BALB/c mice as significantly prolonged, with p values printed as 0.094 and 0.0004 respectively; the first does not meet the stated threshold of p below 0.05
  • Mean peritoneal cancer index was 2.7 in mock-treated AB12 mice versus 1.8 in virus-treated mice, and 2.7 versus 1.6 in AC29 mice
  • Ascites occurred in 20% of AC29 tumour-bearing mice given GLV-0b347 versus 100% of mock-treated animals; no ascites occurred in AB12-bearing BALB/c mice under either treatment
• The authors' conclusion: The authors concluded that intraperitoneal GLV-0b347 prolonged survival, reduced tumour load and ascites in their murine models, but only in animals with limited tumour burden at the time of virus application, and that transferability to humans remains unclear
• Limitations the authors state:
  • The authors state the findings are limited by the highly artificial murine model and are not necessarily transferable to patients
  • The first in vivo experiment could not be completed as planned because rapid tumour progression forced premature endpoints in most animals
  • The authors state it is so far unclear why the virus constructs differed in oncolysis and which factors underlie this
  • The authors state it is unclear whether the results are transferable to humans with peritoneal mesothelioma

Topics

Medical terms in this study, explained in our Lexicon: Peritoneal Mesothelioma, Mesothelioma, Peritoneal Cancer Index (PCI), Ascites, Overall Survival, Tumor Burden.

Related studies

• High Oncolytic Activity of a Double-Deleted Vaccinia Virus Copenhagen Strain against Malignant Pleural Mesothelioma — T. Delaunay, J. Nader, et al. (2020)
• Oncolytic vaccinia virus as an adjuvant treatment to cytoreductive surgery for malignant peritoneal mesothelioma — S.A. Acuna, K. Ottolino-Perry, et al. (2014)
• Correlative analysis from a phase I clinical trial of intrapleural administration of oncolytic vaccinia virus (Olvi-vec) in patients with malignant pleural mesothelioma — N.K. Chintala, J.K. Choe, et al. (2023)
• Regional delivery of oncolytic vaccinia virus: it's time for clinical trials — S. Downs-Canner, D.L. Bartlett (2014)
• Potent efficacy signals from systemically administered oncolytic herpes simplex virus (HSV1716) in hepatocellular carcinoma xenograft models — L. Braidwood, K. Learmonth, et al. (2014)
• Personalized Oncolytic Therapy: The Next Step Toward the Successful Clinical Application of Vaccine-Strain Measles Viruses for Cancer Therapy? — T. Peikert (2020)

Browse more research in Cancers, or return to medical research.