AFP-specific immunotherapy impairs growth of autochthonous hepatocellular carcinoma in mice
AFP-specific immunotherapy impairs growth of autochthonous hepatocellular carcinoma in mice
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DOI：
10.1016/j.jhep.2010.06.027
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发表时间：
2011-01-01
影响因子：
25.7
通讯作者：
Conchon, Sophie
中科院分区：
文献类型：
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作者：
Cany, Jeannette;Barteau, Benoit;Conchon, Sophie
背景和目标：在这项研究中，我们已经评估了潜在的抗原特异性免疫治疗对肝细胞癌（HCC）在低肿瘤负荷的条件下，在一个土生土长的HCC model.Methods：二乙基亚硝胺（DEN）注射到婴儿小鼠的结果，在发展中的多结节性肝癌甲胎蛋白（AFP）的重新表达。注射DEN的动物接受由低剂量的用两亲性嵌段共聚物704（DNA-mAFP/704）配制的编码AFP的质粒组成的合成载体的抗原特异性免疫。在4个月和5个月时，在检测到肉眼可见的结节之前，对动物进行处理，并在8个月时处死。评估肿瘤负荷以及肝脏组织学。AFP和MHC I类分子在结节中的表达通过qRT-PCR.Results监测：AFP特异性免疫治疗导致肿瘤大小显著减小（65%）。在从DNAmAFP/704-treated group.Conclusions：这是第一个研究表明抗原特异性免疫治疗在一个土生土长的HCC模型的相关性，其余的结节中测量AFP和MHC I类分子的表达减少。在这种情况下，我们验证了使用的抗肿瘤免疫疗法的基础上接种由低剂量的抗原编码DNA与嵌段共聚物配制的纳米粒子。我们的研究结果证明了这种策略作为辅助免疫治疗的潜力，以降低肝癌患者局部治疗后的复发风险。(C)2010年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background and Aims: In this study, we have assessed the potential of antigen-specific immunotherapy against hepatocellular carcinoma (HCC) in conditions of low tumour burden, in an autochthonous HCC model.Methods: Diethylnitrosamine (DEN) injected into infant mice results in the development of multi-nodular HCC in which alpha-fetoprotein (AFP) is re-expressed. DEN-injected animals received an antigen-specific immunization with a synthetic vector consisting of a low dose of AFP-encoding plasmid formulated with the amphiphilic block copolymer 704 (DNA-mAFP/704). Animals were treated at 4 and 5 months, before macroscopic nodules were detected, and were sacrificed at 8 months. The tumour burden, as well as liver histology, was assessed. AFP and MHC class I molecule expression in the nodules were monitored by qRT-PCR.Results: The AFP-specific immunotherapy led to a significant (65%) reduction in tumour size. The reduced expression of AFP and MHC class I molecules was measured in the remaining nodules taken from the DNAmAFP/704-treated group.Conclusions: This is the first study demonstrating the relevance of antigen-specific immunotherapy in an autochthonous HCC model. In this context, we validated the use of an anti-tumour immunotherapy based on vaccination with nanoparticles consisting of low dose antigen-encoding DNA formulated with a block copolymer. Our results demonstrate the potential of this strategy as adjuvant immunotherapy to reduce the recurrence risk after local treatment of HCC patients. (C) 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.