title: Aerosol administration of a recombinant adenovirus expressing CFTR to cystic fibrosis patients: a phase I clinical trial.
abstract: Ad CFTR, a replication-deficient adenovirus expressing the human cystic fibrosis transmembrane conductance regulator (CFTR), was administered by aerosolization in a single escalating dose to three pairs (cohorts) of cystic fibrosis (CF) patients. Buffer only was administered to the nose and lungs 9-14 days before nasal instillation of virus followed the day after by aerosolization of Ad CFTR to the lung. Nasal doses (defined in terms of viral plaque forming units, pfu) were 10(5), 10(7), and 4 x 10(8), whereas aerosolized doses were 10(7), 10(8), 5.4 x 10(8) for each cohort, respectively. No acute toxic effects were observed in the first 4 weeks after virus treatment. Shedding of infectious Ad CFTR was never detected, whereas detection of vector DNA sequences and CFTR expression demonstrated DNA transfer to the nose and airways of patients. No significant deviations in immunological and inflammatory parameters were observed in serum and in bronchoalveolar lavage (BAL). Importantly, for all patients, the serum anti-adenovirus antibody levels did not change significantly from baseline and no antibodies against adenovirus were found in BAL.
authors.affiliation: Hospices Civils, Lyon, France.
authors.forename: G
authors.initials: G
authors.lastname: Bellon
authors.forename: L
authors.initials: L
authors.lastname: Michel-Calemard
authors.forename: D
authors.initials: D
authors.lastname: Thouvenot
authors.forename: V
authors.initials: V
authors.lastname: Jagneaux
authors.forename: F
authors.initials: F
authors.lastname: Poitevin
authors.forename: C
authors.initials: C
authors.lastname: Malcus
authors.forename: N
authors.initials: N
authors.lastname: Accart
authors.forename: M P
authors.initials: MP
authors.lastname: Layani
authors.forename: M
authors.initials: M
authors.lastname: Aymard
authors.forename: H
authors.initials: H
authors.lastname: Bernon
authors.forename: J
authors.initials: J
authors.lastname: Bienvenu
authors.forename: M
authors.initials: M
authors.lastname: Courtney
authors.forename: G
authors.initials: G
authors.lastname: Döring
authors.forename: B
authors.initials: B
authors.lastname: Gilly
authors.forename: R
authors.initials: R
authors.lastname: Gilly
authors.forename: D
authors.initials: D
authors.lastname: Lamy
authors.forename: H
authors.initials: H
authors.lastname: Levrey
authors.forename: Y
authors.initials: Y
authors.lastname: Morel
authors.forename: C
authors.initials: C
authors.lastname: Paulin
authors.forename: F
authors.initials: F
authors.lastname: Perraud
authors.forename: L
authors.initials: L
authors.lastname: Rodillon
authors.forename: C
authors.initials: C
authors.lastname: Sené
authors.forename: S
authors.initials: S
authors.lastname: So
authors.forename: F
authors.initials: F
authors.lastname: Touraine-Moulin
authors.forename: A
authors.initials: A
authors.lastname: Pavirani
mesh_terms: D000256:Adenoviridae / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000336:Aerosols / Q000627:therapeutic use*; D015139:Blotting, Southern; D018893:Bronchoalveolar Lavage; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000032:analysis; D005260:Female; D015870:Gene Expression / Q000235:genetics; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009297:Nasal Mucosa / Q000166:cytology / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D000336:Aerosols; C505032:CFTR protein, human; D012333:RNA, Messenger; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004247:DNA