AEROSOL ADMINISTRATION OF A RECOMBINANT ADENOVIRUS EXPRESSING CFTR TOCYSTIC-FIBROSIS PATIENTS - A PHASE-I CLINICAL-TRIAL

Ad CFTR, a replication-deficient adenovirus expressing the human cysti c fibrosis transmembrane conductance regulator (CFTR), was administere d by aerosolization in a single escalating dose to three pairs (cohort s) of cystic fibrosis (CF) patients, Buffer only was administered to t he nose and lungs 9-14 days before nasal instillation of virus followe d 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 1 0(8) for each cohort, respectively, No acute toxic effects were observ ed 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 inflammato ry parameters were observed in serum and in bronchoalveolar lavage (BA L), Importantly, for all patients, the serum anti-adenovirus antibody levels did not change significantly from baseline and no antibodies ag ainst adenovirus were found in BAL.