Gene therapy for mesothelioma

Our plain-English summary of Gene therapy for mesothelioma, by A. Vachani, E. Moon, S.M. Albelda (Current Treatment Options in Oncology, 2011).

The study

• Authors: A. Vachani, E. Moon, S.M. Albelda
• Journal: Current Treatment Options in Oncology
• Published: 2011;12(2):173-80
• Type of article: Review
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Mesothelioma represents an especially good target for gene therapy since few effective therapies exist, the disease remained relatively localized until late in its course, the tumor can be accessed relatively easily through the chest wall, and the thin layer of mesothelial cells offers a large surface area for efficient, rapid, and diffuse gene transfer. Gene therapy trials in mesothelioma have shown safety, and some limited evidence of efficacy. We present a review of clinical trials that have been performed in mesothelioma and describe several new approaches currently being pursued.

In plain English

This article was a short review of gene therapy for malignant pleural mesothelioma (MPM); it did not discuss asbestos exposure. The authors summarized earlier clinical trials and briefly reported results from a just-completed trial. In Phase 1 trials by Sterman and colleagues, a suicide gene (HSVtk) was put into the chest, followed by the drug ganciclovir. Gene transfer was shown in 23 of 30 patients; one patient lived seven years and one was still alive after 10 years. A trial by Schwarzenberger and colleagues saw no significant clinical responses. In a vaccinia IL-2 trial in six patients with advanced MPM, no significant tumor regression was seen. A first adenovirus interferon-beta trial, in patients with MPM or metastatic pleural malignancies, showed gene transfer in 7 of 10 patients. A second, two-dose trial included seventeen patients (10 with MPM, 7 with malignant pleural effusions); antibodies against the adenovirus blocked effective gene transfer from the second dose. A third, just-completed interferon-alpha trial reported disease stabilization in half of the subjects. The authors concluded that these trials had shown safety but only intermittent efficacy.

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 of gene therapy in mesothelioma, which also briefly reports results of a just-completed trial
• Who was studied: clinical trials of gene therapy in patients with malignant pleural mesothelioma. Some of these trials also included patients with metastatic pleural malignancies or malignant pleural effusions.
• Exposure: the review covered gene therapy treatments, not asbestos exposure: suicide gene therapy (HSV thymidine kinase with ganciclovir), cytokine gene therapy (IL-2, interferon-beta, interferon-alpha) and gene-modified T cells targeting mesothelin
• Main results:
  • In Phase 1 Ad.HSVtk/ganciclovir trials by Sterman and colleagues, dose-related gene transfer into the tumor was shown in 23 of 30 patients
  • In the same Ad.HSVtk trials, two patients at the higher dose levels survived for long periods
  • In the Phase 1 trial by Schwarzenberger and colleagues, in which PA1-STK cells were placed in the pleura, no significant clinical responses were seen
  • In the vaccinia IL-2 trial in six patients with advanced MPM (Robinson and colleagues), no significant tumor regression was seen
  • In the first Phase 1 adenovirus interferon-beta trial, which included patients with MPM and patients with metastatic pleural malignancies, gene transfer was shown in 7 of the 10 patients
  • The second, two-dose interferon-beta trial included seventeen patients: 10 with MPM and 7 with malignant pleural effusions
  • In that second trial, high levels of antibodies against the adenovirus blocked effective gene transfer from the second dose
  • In the third, just-completed Phase I trial of adenovirus interferon-alpha, disease stabilization was reported in half of the subjects
• The authors' conclusion: The authors concluded that gene therapy trials in MPM had generally shown safety, but only intermittent efficacy

Topics

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

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

Related studies

• Gene therapy for mesothelioma and lung cancer — A. Vachani, E. Moon, et al. (2010)
• Gene therapy approaches for inherited and acquired lung diseases — D.T. Curiel, J.M. Pilewski, et al. (1996)
• Differential sensitivity of thoracic malignant tumors to adenovirus-mediated drug sensitization gene therapy — W.R. Smythe, H.C. Hwang, et al. (1995)
• Gene therapy for lung neoplasms — A. Vachani, E. Moon, et al. (2011)
• Cytokine gene therapy or infusion as treatment for solid human cancer — B.W. Robinson, S.A. Mukherjee, et al. (1998)
• Use of protamine to augment adenovirus-mediated cancer gene therapy — M. Lanuti, C.E. Kouri, et al. (1999)

Browse more research in Current Treatment Options in Oncology, or return to medical research.