Clinical and Immunological Effects in Patients with Advanced Non-Small Cell Lung-Cancer after Vaccination with Dendritic Cells Exposed to an Allogeneic Tumor Cell Lysate

L. Engell-Noerregaard, P. Kvistborg, M. Zocca, A. Pedersen, M. Claesson, A. Mellemgaard
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引用次数: 6

Abstract

Background: We evaluated the clinical and immunological effects of dendritic cell (DC) vaccination of patients with NSCLC. Autologous DCs were pulsed with a MAGE containing allogeneic melanoma cell lysate (MelCancerVac?, Dandrit Biotech,Copenhagen,Denmark). Imiquimod cream, proleukin and celecoxib were used as adjuvants to the vaccines. The objective of the study was to evaluate specific T cell response in vitro by IFNg EliSpot. Secondary objectives were overall survival, response and quality of life (QoL). Results: Twenty-two patients initiated the vaccination program consisting of ten vaccinations. Seven patients remained in stable disease (SD) three months after the first vaccination. After ten vaccinations (six months), four patients still showed SD and continued vaccinations on a monthly basis. These four patients received a total of 12, 16, 26 and 35 vaccinations, respectively. Five patients showed an unexpectedly prolonged survival. The treatment was well tolerated and only minor adverse events were reported. Quality of life did not change during the study period. In four of the seven patients with SD, vaccine-specific T cells were detected by IFNγ EliSpot assays, whereas only one patient with progressive disease (PD) showed vaccine-specific responses. Conclusion: This DC-based vaccine trial has indicated a correlation between vaccine-specific immunity and sustained SD. Furthermore, we observed an unexpectedly prolonged survival in some patients, which may indicate delayed effect of DC vaccination after completion of the treatment. A prospective randomized phase-IIb or -III is needed to further evaluate the use of MelCancerVac? vaccine treatment in patients with progressive NSCLC.
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晚期非小细胞肺癌患者接种树突状细胞暴露于异体肿瘤细胞裂解液后的临床和免疫学效果
背景:我们评估了树突状细胞(DC)疫苗接种对非小细胞肺癌患者的临床和免疫学效果。用含有同种异体黑色素瘤细胞裂解液(MelCancerVac?, Dandrit Biotech,哥本哈根,丹麦)。咪喹莫特乳膏、白介素原和塞来昔布作为疫苗佐剂。本研究的目的是通过IFNg EliSpot评估体外特异性T细胞反应。次要目标是总体生存、反应和生活质量(QoL)。结果:22例患者启动了由10种疫苗组成的疫苗接种计划。7例患者在第一次接种疫苗后3个月病情保持稳定。接种10次疫苗(6个月)后,4例患者仍出现SD,并每月继续接种疫苗。这四名患者分别接受了12、16、26和35次疫苗接种。5名患者意外地延长了生存期。治疗耐受性良好,仅报告了轻微的不良事件。在研究期间,生活质量没有改变。在7名SD患者中,有4名患者通过IFNγ EliSpot检测到疫苗特异性T细胞,而只有1名进展性疾病(PD)患者表现出疫苗特异性应答。结论:这项基于dc的疫苗试验表明,疫苗特异性免疫与持续SD之间存在相关性。此外,我们观察到一些患者的生存期出乎意料地延长,这可能表明DC疫苗接种在治疗完成后延迟了效果。需要一项前瞻性随机iib期或-III期临床试验来进一步评估MelCancerVac?进展性非小细胞肺癌的疫苗治疗
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