Immunization of NSCLC patients with antigen-pulsed immature autologous dendritic cells

被引:67
作者
Hirschowitz, Edward A. [1 ,2 ]
Foody, Terry [1 ]
Hidalgo, Giovanna E. [3 ]
Yannelli, John R. [2 ,3 ]
机构
[1] Univ Kentucky, Albert B Chandler Med Ctr, Div Pulm & Crit Care Med, Lexington, KY 40536 USA
[2] Univ Kentucky, Albert B Chandler Med Ctr, Lexington Veterans Adm Med Ctr, Markey Canc Ctr, Lexington, KY 40536 USA
[3] Univ Kentucky, Albert B Chandler Med Ctr, Lexington Veterans Adm Med Ctr, Dept Microbiol & Immunol, Lexington, KY 40536 USA
关键词
dendritic cell vaccines; lung cancer; NSCLC; clinical trial;
D O I
10.1016/j.lungcan.2007.04.002
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 8.1 X 107 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. Published by Elsevier Ireland Ltd.
引用
收藏
页码:365 / 372
页数:8
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