Novel oncolytic viral therapies in patients with thoracic malignancies

Our plain-English summary of Novel oncolytic viral therapies in patients with thoracic malignancies, by Z. Ahmad, R.A. Kratzke (Oncolytic Virotherapy, 2017).

The study

• Authors: Z. Ahmad, R.A. Kratzke
• Journal: Oncolytic Virotherapy
• Published: 2017;6:1-9
• Type of article: Review
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Oncolytic virotherapy is the use of replication-competent viruses to treat malignancies. The potential of oncolytic virotherapy as an approach to cancer therapy is based on historical evidence that certain viral infections can cause spontaneous remission of both hematologic and solid tumor malignancies. Oncolytic virotherapy may eliminate cancer cells through either direct oncolysis of infected tumor cells or indirect immune-mediated oncolysis of uninfected tumor cells. Recent advances in oncolytic virotherapy include the development of a wide variety of genetically attenuated RNA viruses with precise cellular tropism and the identification of cell-surface receptors that facilitate viral transfer to the tissue of interest. Current research is also focused on targeting metastatic disease by sustaining the release of progeny viruses from infected tumor cells and understanding indirect tumor cell killing through immune-mediated mechanisms of virotherapy. The purpose of this review is to critically evaluate recent evidence on the clinical development of tissue-specific viruses capable of targeting tumor cells and eliciting secondary immune responses in lung cancers and mesothelioma.

In plain English

Two authors from the University of Minnesota reviewed oncolytic virotherapy, the use of replication-competent viruses, for lung cancers and malignant pleural mesothelioma, covering laboratory, animal and early clinical work and listing trials under way. Among the studies summarised: the chimeric adenovirus Ad5/3-D24-GMCSF, tested in hamsters and in 21 patients with advanced metastatic solid tumours (including NSCLC and mesothelioma), gave stable or better disease control in 67% of patients on radiological assessment, with a positive serum viral titre in 12 of 15 patients; in a Phase I trial of Seneca Valley virus SVV-001 in 30 patients, six with small-cell lung cancer, no patient met RECIST criteria for partial or complete response, although one patient with chemorefractory SCLC had 10 months of progression-free survival; and in mouse mesothelioma xenografts median survival was 65 and 60 days with MV-mIFNb and MV-mIFN-NIS versus 20 days with PBS controls (P less than 0.001). Citing other work, the review stated that asbestos exposure of two months can lead to malignant mesothelioma after many years. The authors concluded that replication-competent viruses show great promise for thoracic cancers, with hurdles remaining, including eluding the host immune system.

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 early clinical studies of oncolytic viruses
• Who was studied: Not an original patient study: the review covered in vitro work, animal models (nude mice, hamsters, orthotopic mouse mesothelioma) and early-phase clinical trials in non-small-cell lung cancer, small-cell lung cancer and malignant pleural mesothelioma; authors based at the University of Minnesota Medical School, published 2017
• Exposure: Oncolytic (replication-competent) viruses: coxsackievirus B3, chimeric adenovirus Ad5/3-D24-GMCSF, Seneca Valley virus SVV-001, measles virus (Edmonston and Schwarz strains, MV-mIFNb, MV-mIFNb-NIS) and Newcastle disease virus; not asbestos
• Main results:
  • Ad5/3-D24-GMCSF was tested in hamsters and in 21 patients with advanced metastatic solid tumours, including NSCLC and mesothelioma, resistant to standard treatment
  • In that patient series, stable or better disease control was reported in 67% of patients on radiological assessment
  • A positive viral titre was found in the serum of 12 of 15 patients given Ad5/3-D24-GMCSF, from days 3 to 7 and also on day 58
  • In the Phase I trial of SVV-001, 30 patients including six with SCLC received the lowest intravenous dose; no significant dose-limiting toxicities were seen
  • No SVV-001 patient achieved a partial or complete response by RECIST; one patient with chemorefractory SCLC had 10 months of progression-free survival and remained alive over 3 years
  • In mouse mesothelioma xenografts, median survival was 65 days with MV-mIFNb and 60 days with MV-mIFN-NIS, compared with 45 days for MV-GFP and MV-GFP-NIS and 20 days for PBS controls
  • In an orthotopic mouse model of malignant pleural mesothelioma, multiple intrapleural doses of NDV (F3aa)-GFP gave a survival benefit over a single dose, with no survival difference by treatment start day
  • Background statement in the review, citing other work, on asbestos and mesothelioma latency
• The authors' conclusion: The authors concluded that replication-competent viruses show great promise for treating thoracic cancers, while critical hurdles remain, and that the role of these therapies will become clearer when ongoing clinical studies are completed
• Limitations the authors state:
  • The authors noted that the preclinical measles virus studies did not address neutralizing antimeasles antibodies from prior infection or vaccination
  • The authors noted that tumour marker levels are of limited use during oncolytic therapy because they can rise from viral replication and tumour cell lysis

Topics

Medical terms in this study, explained in our Lexicon: Lung Cancer, Mesothelioma.

Related studies

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• Novel patterns of progression upon immunotherapy in other thoracic malignancies and uncommon populations — R. Ferrara, D. Signorelli, et al. (2021)
• Novel platinum agents and mesenchymal stromal cells for thoracic malignancies: state of the art and future perspectives — F. Petrella, I. Rimoldi, et al. (2018)
• Tunneling nanotubes: an alternate route for propagation of the bystander effect following oncolytic viral infection — J. Ady, V. Thayanithy, et al. (2016)
• Oncolytic Viral Therapy for Malignant Pleural Mesothelioma — H. Yang, D. Xu, et al. (2020)
• Reply to: Oncolytic Viral Therapy for Malignant Pleural Mesothelioma — D. Jean, T. Delaunay, et al. (2020)

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