A trial of intrapleural adenoviral-mediated Interferon-α2b gene transfer for malignant pleural mesothelioma.
Enviado por Luis Montaner el
Título | A trial of intrapleural adenoviral-mediated Interferon-α2b gene transfer for malignant pleural mesothelioma. |
Publication Type | Journal Article |
Year of Publication | 2011 |
Autores | Sterman, DH, Haas, A, Moon, E, Recio, A, Schwed, D, Vachani, A, Katz, SI, Gillespie, CT, Cheng, G, Sun, J, Papasavvas, E, Montaner, LJ, Heitjan, DF, Litzky, L, Friedberg, J, Culligan, M, June, CH, Carroll, RG, Albelda, SM |
Journal | Am J Respir Crit Care Med |
Volume | 184 |
Issue | 12 |
Pagination | 1395-9 |
Date Published | 2011 Dec 15 |
ISSN | 1535-4970 |
Palabras clave | Adenoviridae, Aged, Aged, 80 and over, Feasibility Studies, Female, Gene Transfer Techniques, Genetic Therapy, Genetic Vectors, Humans, Immunologic Factors, Interferon-alpha, Male, Mesothelioma, Middle Aged, Multimodal Imaging, Pilot Projects, Pleural Neoplasms, Positron-Emission Tomography, Recombinant Proteins, Tomography, X-Ray Computed |
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. Anti-tumor 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-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). |
DOI | 10.1164/rccm.201103-0554CR |
Alternate Journal | Am. J. Respir. Crit. Care Med. |
PubMed ID | 21642245 |
PubMed Central ID | PMC3262033 |
Grant List | P01 CA66726 / CA / NCI NIH HHS / United States P30-ES013508 / ES / NIEHS NIH HHS / United States U01AI065279 / AI / NIAID NIH HHS / United States |