Autologous dendritic cell vaccines for non-small-cell lung cancer
Autologous dendritic cell vaccines for non-small-cell lung cancer
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DOI：
10.1200/jco.2004.01.074
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发表时间：
2004-07-15
影响因子：
45.3
通讯作者：
Yannelli, J
中科院分区：
文献类型：
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作者：
Hirschowitz, EA;Foody, T;Yannelli, J
目的明确治疗的非小细胞肺癌（NSCLC）的治疗效果差得令人无法接受。大量的临床前信息和少量的临床信息表明，树突状细胞（DC）疫苗具有治疗潜力。只有少数非小细胞肺癌患者被纳入DC临床试验。我们为16例接受手术、放化疗或多模式治疗的IA期至IIIB期NSCLC患者提供了自体DC疫苗。该研究的目的是评估异质组非小细胞肺癌患者对DC疫苗的耐受性和免疫反应。方法用过表达Her2/neu、CEA、WT1、Mage2和survivin的异基因非小细胞肺癌细胞系的凋亡小体脉冲CD14+前体制备DC疫苗。树突状细胞在一种诱导表面分子表达的因子的作用下部分成熟，但细胞因子的产生很少。个体皮内免疫2次，间隔1个月。在16周内连续抽取外周血，用干扰素- γ ELISPOT检测免疫应答。结果无意外及严重不良事件发生。免疫反应遵循三种不同的反应模式：(1)16例患者中有5例没有明显的免疫反应，(2)16例患者中有5例表现出肿瘤抗原非依赖性反应，(3)16例患者中有6例表现出抗原特异性反应。免疫反应与分期和既往治疗无关。有利和不利的临床结果与测量的免疫反应无关。结论疫苗在多种非小细胞肺癌患者中具有良好的耐受性和生物活性。建立一个最佳的方法需要在明确的非小细胞肺癌患者群体中进行比较研究。(C) 2004年由美国临床肿瘤学会出版。
Purpose Therapeutic outcomes of definitively treated non-small-cell lung cancer (NSCLC) are unacceptably poor. A wealth of preclinical information, and a modest amount of clinical information indicate that dendritic cell (DC) vaccines have therapeutic potential. Only a handful of NSCLC patients have been included in DC clinical trials. We delivered autologous DC vaccines to 16 individuals with stage IA to IIIB NSCLC treated with surgery, chemoradiation, or multimodality therapy. The objectives of the study were to evaluate tolerability and measure immunologic responses to DC vaccines in a heterogeneous group of NSCLC patients.Methods DC vaccines were generated from CD14+ precursors, pulsed with apoptotic bodies of an allogeneic NSCLC cell line that overexpressed Her2/neu, CEA, WT1, Mage2, and survivin. DCs were partially matured with a factor that induced surface molecule expression but minimal cytokine production. Individuals were immunized intradermally two times, 1 month apart. Peripheral blood was drawn serially over 16 weeks, and immune responses were measured by interferon-gamma ELISPOT.Results There were no unanticipated or serious adverse events. Immunologic responses followed three distinct patterns of reactivity: (1) five of 16 patients showed no clear immunologic response, (2) five of 16 patients showed a tumor-antigen independent response, and (3) six of 16 show an antigen specific response. Immunologic responses were independent of stage and prior therapy. Favorable and unfavorable clinical outcomes were independent of measured immunologic responses.Conclusion Vaccines were well tolerated and had biologic activity in a variety of NSCLC patients. Establishing an optimal approach will require comparative studies in well-defined NSCLC patient groups. (C) 2004 by American Society of Clinical Oncology.