Bellon G, Michel-Calemard L, Thouvenot D, Jagneaux V, Poitevin F, Malcus C, Accart N, Layani M P, Aymard M, Bernon H, Bienvenu J, Courtney M, Döring G, Gilly B, Gilly R, Lamy D, Levrey H, Morel Y, Paulin C, Perraud F, Rodillon L, Sené C, So S, Touraine-Moulin F, Pavirani A
Hospices Civils, Lyon, France.
Hum Gene Ther. 1997 Jan 1;8(1):15-25. doi: 10.1089/hum.1997.8.1-15.
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.
将表达人囊性纤维化跨膜传导调节因子（CFTR）的复制缺陷型腺病毒（Ad CFTR）以单次递增剂量雾化给药于三对（三个队列）囊性纤维化（CF）患者。在经鼻滴注病毒前9 - 14天，仅将缓冲液施用于鼻腔和肺部，次日随后将Ad CFTR雾化至肺部。鼻内剂量（以病毒噬斑形成单位，即pfu定义）分别为10⁵、10⁷和4×10⁸，而每个队列的雾化剂量分别为10⁷、10⁸、5.4×10⁸。在病毒治疗后的前4周未观察到急性毒性作用。从未检测到有感染性的Ad CFTR脱落，而载体DNA序列检测和CFTR表达表明DNA已转移至患者的鼻腔和气道。在血清和支气管肺泡灌洗（BAL）中未观察到免疫和炎症参数有显著偏差。重要的是，对于所有患者，血清抗腺病毒抗体水平与基线相比无显著变化，且在BAL中未发现抗腺病毒抗体。
