New approaches for mesothelioma: biologics, vaccines, gene therapy, and other novel agents

Our plain-English summary of New approaches for mesothelioma: biologics, vaccines, gene therapy, and other novel agents, by A.K. Nowak, R.A. Lake, H.L. Kindler, et al (Seminars in Oncology, 2002).

The study

• Authors: A.K. Nowak, R.A. Lake, H.L. Kindler, B.W. Robinson
• Journal: Seminars in Oncology
• Published: 2002;29(1):82-96
• Type of article: Review
• Cited by: 97 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Although malignant mesothelioma is not a classically immunogenic cancer, there is abundant evidence for immune recognition. The relative ease of obtaining tumor tissue makes mesothelioma ideal for studying surrogate biomarkers such as lymphocytic infiltration or expression of transduced genes. There is evidence that malignant mesothelioma patients as well as asbestos-exposed persons without mesothelioma have impaired immune responsiveness. Substantial progress has been made in animal models using several biological and immunological techniques, but clinical application has been problematic. Systems studied have included lysis by interleukin-2 (IL-2)-activated lymphokine-activated killer (LAK) cells, tumor necrosis factor-alpha (TNF-alpha), a p16-expressing adenovirus vector, suicide gene therapy using the herpes simplex virus-tyrosine kinase (HSV-tk) followed by ganciclovir, and immunomodulatory gene therapy with IL-2, IL-4, interferon-gamma (IFN-gamma), IFN-alpha, TNF-alpha, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6, and IL-1beta transfected into tumors. Vaccinia virus has been studied as a vector for cytokine gene transfer. Suicide gene therapy has been combined with a tumor vaccine. The University of Western Australia is initiating a pilot study of autologous vaccination in malignant mesothelioma. Novel agents under study include the angiogenesis inhibitors SU5416, bevacizumab, and thalidomide. ZD1839, an orally administered, highly selective inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, is being tested in a phase II trial. Since platelet-derived growth factor (PDGF) is thought to be an autocrine growth factor for mesothelioma STI-571 (Gleevec; Novartis, Basel, Switzerland), a highly selective inhibitor of the PDGF receptor tyrosine kinase, is being tested in a phase II trial. The development of more active cytotoxic combinations in this disease should facilitate further studies of chemoimmunotherapy. It seems likely that no single treatment modality will be effective by itself.

Copyright 2002 by W.B. Saunders Company.

In plain English

This article was a review. The authors outlined the laboratory and animal research behind experimental treatments for malignant mesothelioma and reviewed clinical trials of immunotherapy, gene therapy, vaccines, chemoimmunotherapy and new targeted drugs. Citing other studies, they described evidence that mesothelioma patients, and asbestos-exposed people without mesothelioma, have impaired immune responsiveness. In one trial they reviewed, by Boutin and colleagues, 89 patients received interferon-gamma into the pleural space and the overall response rate was 20%. The authors said single-agent interferons had otherwise mostly been abandoned. In a phase I gene therapy trial, gene transfer was shown in 17 of 25 evaluable patients, and median survival of all patients was 11 months. In a nonrandomized trial by Metintas and colleagues, 43 patients given chemoimmunotherapy had a 23% response rate. There was no survival difference from 19 patients who refused treatment and received supportive care. The authors also described a planned 11-patient vaccine pilot study and trials of drugs such as bevacizumab and thalidomide. The authors concluded that no single treatment was likely to be effective by itself.

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 research on experimental mesothelioma treatments
• Who was studied: No study population of its own; the review covered published and unpublished cell-line, animal-model and clinical-trial work on malignant mesothelioma
• Exposure: Not an exposure study; the subject was experimental treatments. Citing other work, the review noted impaired immune responsiveness in asbestos-exposed persons without mesothelioma. No fiber types were specified.
• Main results:
  • Reviewed trial (Boutin et al): 89 patients given intrapleural interferon-gamma had an overall response rate of 20%, including eight histologically confirmed complete responses; the response rate was 45% for Butchart stage I disease
  • The authors reported that clinical trials of interferons were disappointing and caused significant toxicities, and that single-agent interferons had mostly been abandoned
  • Reviewed pilot study of intrapleural IL-2 with lymphokine-activated killer (LAK) cells: no responses were seen
  • Reviewed pilot trial of GM-CSF infused into the tumor in 14 patients with stage II disease: one partial response
  • Reviewed phase I trial of intrapleural adenovirus-delivered HSV-tk gene therapy in 26 patients: gene transfer was shown in 17 of 25 evaluable patients
  • In the same gene therapy trial, median survival of all patients was 11 months
  • Reviewed nonrandomized trial (Metintas et al): 43 patients received cisplatin, mitomycin and interferon-alpha, and 19 who refused treatment received supportive care. The treated group had a 23% response rate, with no survival difference between the groups.
  • Reviewed study (Govindan et al): EGFR was overexpressed in 11 of 13 epithelioid, two of four biphasic and one of seven sarcomatoid mesothelioma specimens
• The authors' conclusion: The authors concluded that, in patients, evaluation of these novel therapies was still in its infancy, and that no single treatment modality was likely to be effective by itself

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, Malignant Mesothelioma, Biomarker, Tumor Necrosis Factor-alpha (TNF-α), Macrophage, Cytokine, Angiogenesis, Bevacizumab.

Related studies

• 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 for malignant pleural mesothelioma: present and future — Y. Tada, Y. Takiguchi, et al. (2008)
• Gene therapy for lung diseases: development in the vector biology and novel concepts for gene therapy applications — M. Suzuki, T. Matsuse, et al. (2001)
• Systemic approach to malignant pleural mesothelioma: what news of chemotherapy, targeted agents and immunotherapy? — D. Signorelli, M. Macerelli, et al. (2016)

Browse more research in Seminars in Oncology, or return to medical research.