A potential therapeutic strategy for malignant mesothelioma with gene medicine

Our plain-English summary of A potential therapeutic strategy for malignant mesothelioma with gene medicine, by Y. Tada, H. Shimada, K. Hiroshima, et al (BioMed Research International, 2013).

The study

• Authors: Y. Tada, H. Shimada, K. Hiroshima, M. Tagawa
• Journal: BioMed Research International
• Published: 2013;2013:572609
• Type of article: Review
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma, closely linked with occupational asbestos exposure, is relatively rare in the frequency, but the patient numbers are going to increase in the next few decades all over the world. The current treatment modalities are not effective in terms of the overall survival and the quality of life. Mesothelioma mainly develops in the thoracic cavity and infrequently metastasizes to extrapleural organs. A local treatment can thereby be beneficial to the patients, and gene therapy with an intrapleural administration of vectors is one of the potential therapeutics. Preclinical studies demonstrated the efficacy of gene medicine for mesothelioma, and clinical trials with adenovirus vectors showed the safety of an intrapleural injection and a possible involvement of antitumor immune responses. Nevertheless, low transduction efficiency remains the main hurdle that hinders further clinical applications. Moreover, rapid generation of antivector antibody also inhibits transgene expressions. In this paper, we review the current status of preclinical and clinical gene therapy for malignant mesothelioma and discuss potential clinical directions of gene medicine in terms of a combinatory use with anticancer agents and with immunotherapy.

In plain English

This article was a review, not an original study. The authors reviewed laboratory, animal and clinical research on gene therapy for malignant mesothelioma, a cancer they described as associated with occupational asbestos exposure in most cases. They summarized five major clinical trials reported by others: three phase I and two pilot studies, using non-replicating adenovirus or vaccinia virus vectors. According to the review, about 60 patients received adenovirus injected into the pleural cavity, and none of them showed severe adverse events. However, the virus spread only around the injection sites or in a surface region, and overall clinical responses were not significant. A few patients had a good clinical outcome several months later. Patients also produced neutralizing antibody against the virus. The authors noted that gene therapy with oncolytic (cancer-killing) viruses had not yet been clinically tested in mesothelioma patients. The authors concluded that gene therapy remained an experimental approach for mesothelioma and should be combined with other conventional treatments rather than used alone.

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 gene therapy research for malignant mesothelioma
• Who was studied: Published preclinical studies and five major clinical gene therapy trials in mesothelioma reported by other researchers (3 phase I and 2 pilot studies)
• Exposure: Not an asbestos exposure study. Asbestos is mentioned only as background: the authors state mesothelioma is associated with occupational asbestos exposure in most cases. The subject reviewed is gene therapy using virus vectors.
• Main results:
  • The clinical trials reviewed used non-replicating adenovirus (3 phase I and 1 pilot study) and vaccinia virus (1 pilot study)
  • Genes delivered in the reviewed trials included HSV-thymidine kinase, interleukin-2, and interferon-alpha and interferon-beta
  • In the reviewed trials, about 60 patients received intrapleural adenovirus, and none showed severe adverse events
  • In the reviewed trials, viral spread was limited to the injection sites or a surface region, and overall clinical responses were reported as not significant
  • The reviewed trials reported a few patients with a good clinical outcome several months after adenovirus administration
  • Neutralizing antibody against the adenovirus was produced after intrapleural administration
  • Gene therapy with oncolytic viruses had not yet been clinically tested in mesothelioma patients
• The authors' conclusion: The authors concluded that gene therapy remains an experimental approach for mesothelioma and should be combined with other conventional treatments rather than used as a monotherapy

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Asbestos Exposure, Overall Survival, Quality of Life, Mesothelioma, Metastasis, Clinical Trial, Immunotherapy.

Related studies

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• Use of protamine to augment adenovirus-mediated cancer gene therapy — M. Lanuti, C.E. Kouri, et al. (1999)
• Adenovirus-mediated wild-type p53 overexpression reverts tumourigenicity of human mesothelioma cells — M. Giuliano, A. Catalano, et al. (2000)
• Differential sensitivity of thoracic malignant tumors to adenovirus-mediated drug sensitization gene therapy — W.R. Smythe, H.C. Hwang, et al. (1995)
• Inhibition of mesothelioma cancer stem-like cells with adenovirus-mediated NK4 gene therapy — X.B. Deng, L. Xiao, et al. (2015)
• Gene therapy for lung diseases: development in the vector biology and novel concepts for gene therapy applications — M. Suzuki, T. Matsuse, et al. (2001)

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