Oncolytic virotherapy for human malignant mesothelioma: recent advances

Our plain-English summary of Oncolytic virotherapy for human malignant mesothelioma: recent advances, by N. Boisgerault, C. Achard, T. Delaunay, et al (Oncolytic Virotherapy, 2015).

The study

• Authors: N. Boisgerault, C. Achard, T. Delaunay, L. Cellerin, F. Tangy, M. Grégoire, J.F. Fonteneau
• Journal: Oncolytic Virotherapy
• Published: 2015;4:133-40
• Type of article: Review
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Cancer virotherapy is an attractive alternative to conventional treatments because it offers a wide range of antitumor effects due to 1) the diversity of the oncolytic viruses that are now available and 2) their multifaceted activities against both tumor cells and tumor vessels, in addition to their ability to induce antitumor immune responses. In this review, we summarize preclinical and clinical data regarding the targeting of malignant mesothelioma (MM) by oncolytic viruses. We also discuss the potential of other oncolytic viruses that have already shown antitumor effects against several malignancies in advanced clinical trials but are yet to be tested against MM cells. Finally, we review how the activation of the immune system and combinations with other types of anticancer treatments could support the development of oncolytic virotherapy for the treatment of MM.

In plain English

This was a narrative review of preclinical and clinical work using oncolytic viruses against human malignant mesothelioma (MM). The authors described MM as an aggressive cancer of the cells lining body cavities, with malignant pleural mesothelioma (MPM) linked to occupational asbestos exposure and diagnosed decades after exposure. They summarised work with herpesviruses (HSV-1716, G207, NV1020, NV1066; T-Vec was described only for melanoma and, the authors stated, had not yet been used in patients with MM), poxviruses (JX-594/Pexa-Vec, GL-ONC1, a vaccinia virus carrying interleukin-2), adenoviruses, and RNA viruses (vesicular stomatitis, measles, Sendai, Newcastle disease, reovirus, retroviral vectors); adenoviral interferon and tumour-suppressor gene transfer was said not to qualify as oncolytic virotherapy per se. In the trials listed, intrapleural delivery of viral vectors was reported as well tolerated; one patient with metastatic MPM given intravenous JX-594 had partial remission over 10 weeks, and one MPM patient given intravenous reovirus with docetaxel had a minor response. The authors concluded that cancer virotherapy is one of the most promising alternatives for MM but that extensive further research and MM-specific trials are needed.

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: narrative review of preclinical and clinical studies, with a table of completed and ongoing clinical trials
• Who was studied: Published preclinical studies (human MM cell lines, mouse xenograft and orthotopic models) and clinical trials in patients with malignant mesothelioma, mostly malignant pleural mesothelioma; trials listed enrolled from 1 to 21 MM patients each
• Exposure: Treatment with oncolytic viruses (herpesviruses, poxviruses/vaccinia, adenoviruses, vesicular stomatitis virus, measles virus, Sendai virus, Newcastle disease virus, reovirus, retroviral vectors), given intratumorally, intrapleurally or intravenously, alone or with chemotherapy, radiation, epigenetic drugs or immune checkpoint antibodies; asbestos exposure is mentioned only as the cause of MPM
• Main results:
  • Background figure cited by the review for mesothelioma outcome: survival of about 40% at 1 year after diagnosis and 10% at 5 years
  • The review stated that T-Vec, tested in melanoma, had not been used in MM patients, while other HSV strains had been studied against MM cells
  • The review stated that adenoviral vectors re-expressing p53, p14 or p16 do not qualify as oncolytic virotherapy per se but allowed testing of intrapleural gene delivery
  • In a Phase I study of JX-594 in solid tumours, the single included patient with metastatic MPM had partial remission for more than 10 weeks after one intravenous injection
  • In a reovirus trial, the one patient with metastatic MPM showed viral protein production in infected MPM cells and a decrease in the size of an invaded lymph node after six cycles of docetaxel/reovirus (tabulated as a 23% size decrease for one invaded lymph node)
  • Across adenoviral gene-transfer trials reviewed, intrapleural delivery of viral vectors was reported as well tolerated and able to activate antitumour immune responses
  • In a Phase I trial of an oncolytic adenovirus coding for GM-CSF in solid tumours, of the two MPM patients included one had disease stabilization and the other progressive disease
  • In a Phase I trial of Ad.HSVtk with systemic ganciclovir in 21 MPM patients, the review's table records it as well tolerated with antitumor antibodies and 2 long-term survivors (more than 6.5 years)
  • The authors reported unpublished work of their own group on type I interferon deficiencies in tumour cells from 22 MPM patients as a possible marker of susceptibility to oncolytic measles virus
• The authors' conclusion: The authors concluded that cancer virotherapy is one of the most promising alternatives for mesothelioma, since human MM cells are sensitive to many oncolytic viruses, but that extensive further research and mesothelioma-specific trials are needed
• Limitations the authors state:
  • The authors noted that mesothelioma is often studied only within mixed 'solid tumour' trials containing few MM patients, so MM-specific trials are needed
  • The authors noted that because MM is relatively rare, enrolling large numbers of patients in a single study may be difficult
  • The authors noted that VSV-induced immune responses need further characterization, since the virus can also induce suppressive activity mediated by myeloid-derived suppressor cells

Topics

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

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