Viroimmunotherapy of Thoracic Cancers

Our plain-English summary of Viroimmunotherapy of Thoracic Cancers, by A.S. Dash, M.R. Patel (Biomedicines, 2017).

The study

• Authors: A.S. Dash, M.R. Patel
• Journal: Biomedicines
• Published: 2017;5(1)
• Type of article: Review
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Thoracic cancers, including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and malignant pleural mesothelioma (MM), cause the highest rate of cancer mortality worldwide. Most of these deaths are as a result of NSCLC; however, prognoses for the other two diseases remain as some of the poorest of any cancers. Recent advances in immunotherapy, specifically immune checkpoint inhibitors, have begun to help a small population of patients with advanced lung cancer. People who respond to these immune therapies generally have a durable response and many see dramatic decreases in their disease. However, response to immune therapies remains relatively low. Therefore, intense research is now underway to rationally develop combination therapies to expand the range of patients who will respond to and benefit from immune therapy. One promising approach is with oncolytic viruses. These oncolytic viruses (OVs) have been found to be selective for or have been engineered to preferentially infect and kill cancer cells. In pre-clinical models of different thoracic cancers, it has been found that these viruses can induce immunogenic cell death, increase the number of immune mediators brought into the tumor microenvironment and broaden the neoantigen-specific T cell response. We will review here the literature regarding the application of virotherapy toward augmenting immune responses in thoracic cancers.

In plain English

This was a narrative review by two authors of published laboratory and clinical work on oncolytic viruses ("viroimmunotherapy") for thoracic cancers: non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC) and malignant pleural mesothelioma. The authors noted that anti-PD1 antibody immunotherapy produces responses in only about 15%-30% of patients, prompting interest in combinations. They tabulated oncolytic viruses studied in these cancers (adenovirus, coxsackievirus, herpes simplex virus, measles virus, Newcastle disease virus, reovirus, vaccinia virus, vesicular stomatitis virus), mostly in cell culture and mouse models, and listed ongoing or completed clinical trials. Among reviewed clinical work, a trial of reovirus with standard chemotherapy in NSCLC patients selected for activation of the epidermal growth factor pathway (listed in the article's table as KRAS or EGFR activation) gave an objective response rate of 31%, which the authors called higher than expected with chemotherapy alone while noting that the lack of a comparator arm limits conclusions; a randomised trial of Seneca Valley Virus SVV-001 in SCLC showed no benefit (reported from presented, unpublished data); and an intrapleural interferon-beta adenovirus gene therapy trial showed antitumour immune responses in seven of 10 patients. The authors concluded that the time has come for clinical testing in thoracic cancers.

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 published preclinical and clinical literature
• Who was studied: Published studies of oncolytic viruses in non-small cell lung cancer, small cell lung cancer and malignant pleural mesothelioma, mostly in vitro and in mouse models, plus a small number of human trials
• Exposure: Treatment with oncolytic viruses, including some engineered to express interferon-beta or GM-CSF, alone or combined with chemotherapy or immune checkpoint blockade
• Main results:
  • In the reviewed reovirus trial, patients had NSCLC with activation of the epidermal growth factor pathway (Table 2 lists KRAS or EGFR activation as an entry requirement)
  • The objective response rate in that reovirus trial was 31%, which the authors said was higher than expected with chemotherapy alone, though the missing comparator arm limited conclusions
  • A randomised phase II trial of SVV-001 in SCLC after induction chemotherapy found no benefit; development for SCLC was stopped
  • In a phase I trial of intrapleural replication-deficient adenovirus expressing IFN-beta for lung cancer with malignant pleural effusion and mesothelioma, antitumour immune responses were seen in seven of 10 patients, with rare clinical responses
  • In mesothelioma models, measles virus engineered to express IFN-beta gave two- to four-fold higher infiltration of CD68 monocytes in athymic mice than the parent virus
  • In murine mesothelioma models of VSV expressing IFN-beta, CD8 depletion removed the antitumour activity
  • The authors reported that response rates to anti-PD1 antibodies in these diseases remain in the range of 15% to 30%
• The authors' conclusion: The authors concluded that preclinical data suggest oncolytic viruses can act as immunotherapy alone and with checkpoint blockade, and that clinical testing in thoracic cancers is now warranted
• Limitations the authors state:
  • Pre-existing neutralising antibodies limit systemic delivery of oncolytic viruses
  • Measles virus does not infect mice, so there is no immune-competent animal model for studying its immune effects
  • Mechanisms of the observed immune effects are not fully worked out
  • Mouse findings may not carry over to humans because of substantial species differences

Topics

Medical terms in this study, explained in our Lexicon: Non-Small Cell Lung Cancer, Small Cell Lung Cancer, Pleural Mesothelioma, Immunotherapy, checkpoint inhibitors, Lung Cancer, Tumor Microenvironment.

Related studies

• Engineered Cellular Therapies for the Treatment of Thoracic Cancers — S.M. Erickson, B.M. Manning, et al. (2024)
• COVID-19 in patients with thoracic malignancies (TERAVOLT): first results of an international, registry-based, cohort study — M.C. Garassino, J.G. Whisenant, et al. (2020)
• Guidelines of the European Respiratory Society and the European Society of Thoracic Surgeons for the management of malignant pleural mesothelioma — A. Scherpereel, P. Astoul, et al. (2010)
• Clinical development of TargomiRs, a miRNA mimic-based treatment for patients with recurrent thoracic cancer — G. Reid, S.C. Kao, et al. (2016)
• British Thoracic Society Guideline for the investigation and management of malignant pleural mesothelioma — I. Woolhouse, L. Bishop, et al. (2018)
• British Thoracic Society study of cryptogenic fibrosing alveolitis: current presentation and initial management. Fibrosing Alveolitis Subcommittee of the Research Committee of the British Thoracic Society — I.D. Johnston, R.J. Prescott, et al. (1997)

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