Gene therapy for malignant pleural mesothelioma: present and future

Our plain-English summary of Gene therapy for malignant pleural mesothelioma: present and future, by Y. Tada, Y. Takiguchi, K. Hiroshima, et al (Oncology Research, 2008).

The study

• Authors: Y. Tada, Y. Takiguchi, K. Hiroshima, H. Shimada, T. Ueyama, M. Nakamura, K. Tatsumi, T. Kuriyama, M. Tagawa
• Journal: Oncology Research
• Published: 2008;17(6):239-46
• Type of article: Review
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma is relatively rare in frequency but one of the intractable diseases linked with asbestos exposure. Clinical outcomes with the present treatment modalities are unsatisfactory and no effective prevention method has been reported. Growing numbers of the patients in the Western countries with a long latent period need development of a novel therapeutic strategy. Gene therapy is a candidate for mesothelioma treatment because of its easy accessibility of a vector-mediated gene medicine into the intrapleural cavity. Several preclinical studies demonstrated that the gene medicine produced antitumor effects, suggesting the feasibility in clinical settings. In this article, we review the current status of gene therapy and clinical trials targeting mesothelioma and address possible directions to improve the efficacy.

In plain English

This article was a review of gene therapy for malignant pleural mesothelioma, a cancer the authors described as linked with asbestos exposure. It did not study asbestos exposure itself. The authors reviewed four clinical trials of gene therapy for this cancer reported in the Western world (three phase I trials and one pilot study), along with laboratory studies. In a University of Pennsylvania phase I trial of an adenovirus carrying a 'suicide' gene (HSVtk) given with the drug ganciclovir, 34 patients were enrolled. Gene transfer into tumors was seen in 17 of 25 evaluable patients, and three patients survived more than 5 years. A trial using gene-modified cells was reported as safe. A pilot study of vaccinia virus carrying the IL-2 gene reported no clinical responses. A phase I trial of adenovirus carrying interferon-beta, in 10 cancer patients including 7 with mesothelioma, was judged by its investigators to be feasible and well tolerated. The authors noted that patient numbers in these trials were limited. They concluded that the efficacy of gene therapy was currently not optimal and suggested combining it with conventional or immune-based treatments.

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: Review of clinical trials and preclinical (laboratory and animal) studies of gene therapy for malignant pleural mesothelioma
• Who was studied: Published gene therapy studies for malignant pleural mesothelioma (MPM). These were four clinical trials conducted in the Western world (three phase I trials and one pilot study) plus preclinical studies. The review was published in 2008.
• Exposure: Asbestos exposure was not studied. The article mentions asbestos only as background, describing MPM as linked with asbestos exposure. The 'exposures' reviewed were gene therapy treatments: an HSVtk suicide gene with ganciclovir, interferon-beta, IL-2 delivered by vaccinia virus, and other experimental approaches.
• Main results:
  • In the reviewed University of Pennsylvania phase I trial of an adenovirus carrying the HSVtk gene (Ad-HSVtk) followed by ganciclovir, 34 patients without prior chemotherapy were enrolled.
  • In that trial, successful gene transfer into the tumors was observed in 17 of 25 evaluable patients.
  • In that trial, three cases survived more than 5 years. The authors noted that efficacy was not the purpose of the phase I study.
  • In the reviewed phase I trial by Harrison et al., gene-modified ovarian cancer cells expressing HSVtk were given into the chest cavity. The cell-based gene therapy was reported as safe, but precise clinical results and outcomes were not reported.
  • In the reviewed pilot study of vaccinia virus carrying IL-2 injected into tumors, no major toxicities were reported, and no clinical responses were observed.
  • The reviewed phase I trial of a single injection of adenovirus carrying interferon-beta (Ad-IFN-β) into the chest cavity included 10 cancer patients, 7 of whom had MPM.
  • In the Ad-IFN-β trial, some MPM patients showed prolonged survival (more than 26 months) after treatment, although the gene therapy had been combined with conventional chemotherapy.
  • The investigators of the Ad-IFN-β trial concluded that a single intrapleural injection was feasible and well tolerated.
• The authors' conclusion: The authors concluded that the efficacy of gene therapy was currently not optimal for a therapeutic modality. They suggested using it in combination with conventional therapy or as an adjuvant, and presumed that combination with immune responses was the most promising strategy.
• Limitations the authors state:
  • The authors stated that only four clinical studies at a phase I level had been reported and that patient numbers were limited, so comparing efficacy with other cancers was inappropriate.
  • For the Ad-HSVtk trial, the authors noted that clinical outcomes were difficult to evaluate and that efficacy was not a purpose of the phase I study.

Topics

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

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

Related studies

• Gene therapy for malignant mesothelioma: current prospects and challenges — M. Tagawa, Y. Tada, et al. (2013)
• Gene therapy for mesothelioma and lung cancer — A. Vachani, E. Moon, et al. (2010)
• Mesothelioma: an inviting but challenging target for gene therapy — R.G. Crystal (2010)
• Chemotherapy delivered after viral immunogene therapy augments antitumor efficacy via multiple immune-mediated mechanisms — Z.G. Fridlender, J. Sun, et al. (2010)
• Gene therapy using adenovirus carrying the herpes simplex-thymidine kinase gene to treat in vivo models of human malignant mesothelioma and lung cancer — H.C. Hwang, W.R. Smythe, et al. (1995)
• Replication-restricted vaccinia as a cytokine gene therapy vector in cancer: persistent transgene expression despite antibody generation — S. Mukherjee, T. Haenel, et al. (2000)

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