title: A trial of intrapleural adenoviral-mediated Interferon-α2b gene transfer for malignant pleural mesothelioma.
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).
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, University of Pennsylvania Medical Center, Philadelphia, 19104-4283, USA. Daniel.Sterman@uphs.upenn.edu
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Sterman
authors.forename: Andrew
authors.initials: A
authors.lastname: Haas
authors.forename: Edmund
authors.initials: E
authors.lastname: Moon
authors.forename: Adriana
authors.initials: A
authors.lastname: Recio
authors.forename: Daniel
authors.initials: D
authors.lastname: Schwed
authors.forename: Anil
authors.initials: A
authors.lastname: Vachani
authors.forename: Sharyn I
authors.initials: SI
authors.lastname: Katz
authors.forename: Colin T
authors.initials: CT
authors.lastname: Gillespie
authors.forename: Guanjun
authors.initials: G
authors.lastname: Cheng
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Papasavvas
authors.forename: Luis J
authors.initials: LJ
authors.lastname: Montaner
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Heitjan
authors.forename: Leslie
authors.initials: L
authors.lastname: Litzky
authors.forename: Joseph
authors.initials: J
authors.lastname: Friedberg
authors.forename: Melissa
authors.initials: M
authors.lastname: Culligan
authors.forename: Carl H
authors.initials: CH
authors.lastname: June
authors.forename: Richard G
authors.initials: RG
authors.lastname: Carroll
authors.forename: Steven M
authors.initials: SM
authors.lastname: Albelda
mesh_terms: D000256:Adenoviridae; D000368:Aged; D000369:Aged, 80 and over; D005240:Feasibility Studies; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000009:adverse effects; D005822:Genetic Vectors; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000235:genetics; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000235:genetics; D008297:Male; D008654:Mesothelioma / Q000000981:diagnostic imaging / Q000276:immunology / Q000628:therapy*; D008875:Middle Aged; D064847:Multimodal Imaging; D010865:Pilot Projects; D010997:Pleural Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology / Q000628:therapy*; D049268:Positron-Emission Tomography; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics; D014057:Tomography, X-Ray Computed
chemical_list: D007155:Immunologic Factors; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins