A Trial of Intrapleural Adenoviral-mediated Interferon-alpha 2b Gene Transfer for Malignant Pleural Mesothelioma

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

来源：American Journal of Respiratory and Critical Care Medicine, 2011, 184(12): 1395-1399.

DOI：10.1164/rccm.201103-0554CR

• clinical trials
• immunotherapy
• gene therapy

New therapeutic strategies are needed for malignant pleural mesothelioma (MPM). We conducted a single-center, open-label, non-randomized, pilot and feasibility trial using two intrapleural doses of an adenoviral vector encoding human IFN-alpha (Ad.IFN-alpha 2b). Nine subjects were enrolled at two dose levels. The first three subjects had very high pleural and systemic IFN-alpha concentrations resulting in severe "flu-like" symptoms necessitating dose de-escalation. The next six patients had reduced (but still significant) pleural and serum IFN-alpha levels, but with tolerable symptoms. Repeated vector administration appeared to prolong IFN-alpha 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, evidence of disease stability or tumor regression was seen in the remaining five patients, including one dramatic example of partial tumor regression at sites not in contiguity with vector infusion. These data show that Ad.IFN-alpha 2bhas potential therapeutic benefit in MPM and that it generates anti-tumor immune responses that may induce anatomic and/or metabolic reductions in distant tumor.

• 出版日期2011-12-15