Nemunaitis John, Sterman Daniel, Jablons David, Smith John W, Fox Bernard, Maples Phil, Hamilton Scott, Borellini Flavia, Lin Andy, Morali Sayeh, Hege Kristen
US Oncology, Dallas, TX, USA.
J Natl Cancer Inst. 2004 Feb 18;96(4):326-31. doi: 10.1093/jnci/djh028.
To evaluate the feasibility, safety, and efficacy of vaccination with autologous tumor cells genetically modified with an adenoviral vector (Ad-GM) to secrete human granulocyte-macrophage colony-stimulating factor (GM-CSF), we conducted a phase I/II multicenter trial in patients with early and advanced stage non-small-cell lung cancer (NSCLC). Vaccines were generated from autologous tumor harvests. Intradermal injections were given every 2 weeks for a total of three to six vaccinations. Tumors were harvested from 83 patients, 20 with early-stage NSCLC and 63 with advanced- stage NSCLC; vaccines were successfully manufactured for 67 patients, and 43 patients were vaccinated. The most common toxicity was a local injection-site reaction (93%). Three of 33 advanced-stage patients, two with bronchioloalveolar carcinoma, had durable complete tumor responses (lasting 6, 18, and >or=22 months). Longer survival was observed in patients receiving vaccines secreting GM-CSF at more than 40 ng/24 h per 10(6) cells (median survival = 17 months, 95% confidence interval [CI] = 6 to 23 months) than in patients receiving vaccines secreting less GM-CSF (median survival = 7 months, 95% CI = 4 to 10 months) (P =.028), suggesting a vaccine dose-related survival advantage.
为评估接种经腺病毒载体（Ad-GM）基因改造以分泌人粒细胞-巨噬细胞集落刺激因子（GM-CSF）的自体肿瘤细胞疫苗的可行性、安全性和有效性，我们对早期和晚期非小细胞肺癌（NSCLC）患者开展了一项I/II期多中心试验。疫苗由自体肿瘤样本制备。每2周进行一次皮内注射，共注射三至六次。从83例患者获取肿瘤样本，其中20例为早期NSCLC，63例为晚期NSCLC；成功为67例患者制备了疫苗，43例患者接种了疫苗。最常见的毒性反应是局部注射部位反应（93%）。33例晚期患者中有3例出现持久的完全肿瘤缓解（持续6、18和≥22个月），其中2例为细支气管肺泡癌。与接受分泌GM-CSF量低于40 ng/24 h每10⁶细胞的疫苗的患者（中位生存期 = 7个月，95%置信区间[CI] = 4至10个月）相比，接受分泌GM-CSF量高于40 ng/24 h每10⁶细胞的疫苗的患者观察到更长的生存期（中位生存期 = 17个月，95% CI = 6至23个月）（P = 0.028），提示疫苗剂量与生存优势相关。
