A trial of intrapleural adenoviral-mediated interferon-α2b gene transfer for malignant pleural mesothelioma

Daniel H. Sterman, Andrew Haas, Edmund Moon, Adriana Recio, Daniel Schwed, Anil Vachani, Sharyn I. Katz, Colin T. Gillespie, Guanjun Cheng, Jing Sun, Emmanouil Papasavvas, Luis J. Montaner, Daniel F. Heitjan, Leslie Litzky, Joseph Friedberg, Melissa Culligan, Carl H. June, Richard G. Carrolly, Steven M. Albelda

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

New therapeutic strategies are needed for malignant pleural mesothelioma (MPM). We conducted a single-center, open-label, nonrandomized, pilot and feasibility trial using two intrapleural doses of an adenoviral vector encoding human IFN-α(Ad.IFN-α2b). Nine subjects were enrolled at two dose levels. The first three subjects had very high pleural and systemic IFN-α concentrations resulting in severe "flu-like" symptoms necessitating dose de-escalation. The next six patients had reduced (but still significant) pleural and serum IFN-α levels, but with tolerable symptoms. Repeated vector administration appeared to prolong IFN-α expression levels. Antitumor humoral immune responses against mesothelioma cell lines were seen in seven of the eight subjects evaluated. No clinical responses were seen in the four subjects with advanced disease. However, evidenceof disease stability ortumorregressionwasseen in the remaining five patients, including one dramatic example of partial tumorregression at sites not in contiguity with vector infusion. These data show that Ad.IFN-α2b has potential therapeutic benefit in MPM and that it generates anti-tumor immune responses that may induce anatomic and/or metabolic reductions in distant tumor. Clinical trial registered with www.clinicaltrials.gov (NCT 01212367).

Original languageEnglish (US)
Pages (from-to)1395-1399
Number of pages5
JournalAmerican journal of respiratory and critical care medicine
Volume184
Issue number12
DOIs
StatePublished - Dec 15 2011

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Keywords

  • Clinical trials
  • Gene therapy
  • Immunotherapy

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Sterman, D. H., Haas, A., Moon, E., Recio, A., Schwed, D., Vachani, A., Katz, S. I., Gillespie, C. T., Cheng, G., Sun, J., Papasavvas, E., Montaner, L. J., Heitjan, D. F., Litzky, L., Friedberg, J., Culligan, M., June, C. H., Carrolly, R. G., & Albelda, S. M. (2011). A trial of intrapleural adenoviral-mediated interferon-α2b gene transfer for malignant pleural mesothelioma. American journal of respiratory and critical care medicine, 184(12), 1395-1399. https://doi.org/10.1164/rccm.201103-0554CR