Granulocyte-Macrophage Colony-Stimulating Factor Gene-Modified Autologous Tumor Vaccines in Non-Small-Cell Lung Cancer

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Abstract
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 ≥22 months). Longer survival was observed in patients receiving vaccines secreting GM-CSF at more than 40 ng/24 h per 106 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.