title: Immunization of NSCLC patients with antigen-pulsed immature autologous dendritic cells.
abstract: Only a handful of NSCLC patients have been included in dendritic cell (DC) vaccine clinical trials. We had previously reported a series of 16 individuals with stages IA-IIIB NSCLC who received autologous DC vaccines matured with dendritic cell/T cell-derived maturation factor (DCTCMF). Here we report the results of a continuation study with similar inclusion criteria, immunization protocol, and analysis, using an immature DC vaccine. Of the 14 participants, 7 had undergone surgical resection (stage I/II), with or without adjuvant therapy, and 7 with unresectable stage III had been treated with chemo-radiation alone. Autologous DCs were pulsed with apoptotic bodies derived from an allogeneic NSCLC cell line that over-expresses Her2/neu, CEA, WT1, Mage2, and survivin. DCs were not exposed to any maturation stimulus. Individuals received two intradermal vaccines (average 8.1x10(7) DC per immunization) 1 month apart. Immune responses were measured by IFN-gamma ELISPOT, comparing relative number of antigen-reactive T-cells from pre-vaccine to timepoints post-immunization. Immunologic responses were seen in 4/7 stage III unresectable, and 6/7 stage I/II surgically resected patients, including 3/3 resected patients who had also received adjuvant chemo-radiation. There were no related adverse events. One of seven surgically resected patients recurred and 4/7 stage III patients progressed. Three of five patients with progressive disease showed no immunologic response. Data indicate that immature DC pulsed with apoptotic tumour cells have similar biologic activity to a DCTCMF-matured DC preparation delivered in a similar clinical protocol. Therapeutic efficacy is unknown and clinical outcomes are anecdotal.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, University of Kentucky, Chandler Medical Center, Lexington Veteran's Administration Medical Center, Lexington, KY 40536, USA. eahirs2@email.uky.edu
authors.forename: Edward A
authors.initials: EA
authors.lastname: Hirschowitz
authors.forename: Terry
authors.initials: T
authors.lastname: Foody
authors.forename: Giovanna E
authors.initials: GE
authors.lastname: Hidalgo
authors.forename: John R
authors.initials: JR
authors.lastname: Yannelli
mesh_terms: D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000628:therapy*; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D005260:Female; D006801:Humans; D007114:Immunization; D008175:Lung Neoplasms / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines