Vaccination With Irradiated Autologous Tumor Cells Engineered to Secrete Granulocyte-Macrophage Colony-Stimulating Factor Augments Antitumor Immunity in Some Patients With Metastatic Non–Small-Cell Lung Carcinoma

作者：Ravi Salgia, Thomas James Lynch, Arthur T. Skarin, Joan Vern Lucca, Cathleen Lynch, Ken Jung, Frank Stephen Hodi, Michael T. Jaklitsch, Steve J. Mentzer, Steven Swanson, Jeanne M. Lukanich, Raphael Bueno, John R. Wain, Douglas J. Mathisen, Cameron D. Wright, Panos M. Fidias, Dean M. Donahue, S Clift, Steve Hardy, Donna S Neuberg, Richard C. Mulligan, Iain James Webb, David J. Sugarbaker, Martín C. Mihm, Glenn Dranoff · 发表于：Journal of Clinical Oncology · 年份：2003 · DOI：10.1200/jco.2003.03.091 · 被引用次数：296 · 研究领域：Immunotherapy and Immune Responses、Cancer Research and Treatments、CAR-T cell therapy research

PURPOSE: We demonstrated that vaccination with irradiated tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates potent, specific, and long-lasting antitumor immunity in multiple murine models and patients with metastatic melanoma. To test whether this vaccination strategy enhances antitumor immunity in patients with metastatic non-small-cell lung cancer (NSCLC), we conducted a phase I clinical trial. PATIENTS AND METHODS: Resected metastases were processed to single-cell suspension, infected with a replication-defective adenoviral vector encoding GM-CSF, irradiated, and cryopreserved. Individual vaccines consisted of 1 x 10(6), 4 x 10(6), or 1 x 10(7) cells, depending on overall yield, and were administered intradermally and subcutaneously at weekly and biweekly intervals. RESULTS: Vaccines were successfully manufactured for 34 (97%) of 35 patients. The average GM-CSF secretion was 513 ng/10(6) cells/24 h. Toxicities were restricted to grade 1 to 2 local skin reactions. Nine patients were withdrawn early because of rapid disease progression. Vaccination elicited dendritic cell, macrophage, granulocyte, and lymphocyte infiltrates in 18 of 25 assessable patients. Immunization stimulated the development of delayed-type hypersensitivity reactions to irradiated, dissociated, autologous, nontransfected tumor cells in 18 of 22 patients. Metastatic lesions resected after vaccination showed T lymphocyte and plasma cell infiltrates with ...