Gene therapy for lung neoplasms

Our plain-English summary of Gene therapy for lung neoplasms, by A. Vachani, E. Moon, E. Wakeam, et al (Clinics in Chest Medicine, 2011).

The study

• Authors: A. Vachani, E. Moon, E. Wakeam, A.R. Haas, D.H. Sterman, S.M. Albelda
• Journal: Clinics in Chest Medicine
• Published: 2011;32(4):865-85
• Type of article: Review
• Cited by: 18 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Both advanced-stage lung cancer and malignant pleural mesothelioma are associated with a poor prognosis. Advances in treatment regimens for both diseases have had only a modest effect on their progressive course. Gene therapy for thoracic malignancies represents a novel therapeutic approach and has been evaluated in several clinical trials. Strategies have included induction of apoptosis, tumor suppressor gene replacement, suicide gene expression, cytokine-based therapy, various vaccination approaches, and adoptive transfer of modified immune cells. This review considers the clinical results, limitations, and future directions of gene therapy trials for thoracic malignancies.

Copyright © 2011 Elsevier Inc. All rights reserved.

In plain English

This article was a review, not a new study. The authors reviewed early clinical trials of gene therapy for lung cancer and malignant pleural mesothelioma (MPM). They described MPM as usually presenting in the context of an asbestos exposure history. The approaches reviewed included replacing tumor suppressor genes such as p53, gene-modified tumor vaccines, antisense drugs, suicide genes and cytokine genes. Some reviewed MPM trials put gene-carrying viruses into the pleural space; others injected a virus into chest wall tumors or instilled gene-modified cells. In one series of suicide gene trials, gene transfer was shown in 23 of 30 patients, and two patients had long periods of survival. In a single-dose interferon-beta gene trial in 10 patients (7 with MPM and 3 with other pleural cancers), 4 patients showed disease stability or partial regression at 2 months. In lung cancer, a phase III trial of the antisense drug aprinocarsen did not show enhanced survival. The authors concluded that these trials had generally shown safety but only intermittent efficacy, and that gene therapy had not yet reached clinical practice. They stated their belief that progress was being made.

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 and ongoing clinical trials of gene therapy for thoracic cancers (lung cancer and malignant pleural mesothelioma)
• Who was studied: No new patients were studied. The review covered early-phase (mostly phase I and II) trials in patients with non-small cell lung cancer, small cell lung cancer, bronchioloalveolar carcinoma, malignant pleural mesothelioma and malignant pleural effusions.
• Exposure: No asbestos exposure was studied. The 'exposure' was gene therapy treatment: viral and nonviral vectors, tumor suppressor gene replacement, gene-modified vaccines, antisense therapy, suicide gene therapy and cytokine gene therapy. Asbestos appears only as background: the authors note that MPM usually presents with an asbestos exposure history.
• Main results:
  • Some reviewed MPM trials delivered a viral vector into the pleural space, for example Ad.IFN-b given through an indwelling pleural catheter.
  • One reviewed MPM trial injected a vaccinia virus carrying the IL-2 gene into chest wall tumors of 6 patients.
  • Another reviewed MPM trial instilled gene-modified ovarian cancer cells (PA1-STK cells), rather than a virus, into the pleural space.
  • In the reviewed phase I trials of Ad.HSVtk/ganciclovir suicide gene therapy in patients with advanced MPM, dose-related gene transfer into the tumor was shown in 23 of 30 patients.
  • In the same MPM suicide gene trials, two patients had long periods of survival, one of them still alive after 10 years.
  • In a reviewed phase I trial of a single dose of Ad.IFN-b in 7 patients with MPM and 3 with metastatic pleural malignancies, 4 patients showed disease stability or partial regression 2 months after treatment.
  • In a reviewed second Ad.IFN-b trial in 17 patients (10 with MPM, 7 with malignant pleural effusions), high levels of antibodies against the adenovirus blocked effective gene transfer of the second dose.
  • In a reviewed phase III lung cancer trial, adding the antisense drug aprinocarsen to chemotherapy did not show enhanced survival.
• The authors' conclusion: The authors concluded that gene therapy trials for thoracic cancers had generally shown safety but only intermittent efficacy, and that gene therapy for lung cancer and MPM had not yet reached clinical practice. They stated their belief that progress was being made.
• Limitations the authors state:
  • The authors state that with the vectors then available, it was difficult to get genes into more than a small percentage of tumor cells, usually only by local injection.

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: Neoplasm, Lung Cancer, Pleural Mesothelioma, Prognosis, Clinical Trial, Apoptosis, Tumor Suppressor Gene, Cytokine.

Related studies

• Gene therapy for mesothelioma and lung cancer — A. Vachani, E. Moon, et al. (2010)
• Gene therapy for mesothelioma — A. Vachani, E. Moon, et al. (2011)
• 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)
• 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)
• 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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