静脉注射编码NY-ESO-1的慢病毒载体可诱导有效的细胞毒性T淋巴细胞（CTL）反应。

Intravenous injection of a lentiviral vector encoding NY-ESO-1 induces an effective CTL response.

作者信息

Palmowski Michael J, Lopes Luciene, Ikeda Yasuhiro, Salio Mariolina, Cerundolo Vincenzo, Collins Mary K

机构信息

Tumour Immunology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom.

出版信息

J Immunol. 2004 Feb 1;172(3):1582-7. doi: 10.4049/jimmunol.172.3.1582.

DOI:10.4049/jimmunol.172.3.1582

PMID:14734738

Abstract

Lentiviral vectors can efficiently transduce a variety of nondividing cells, including APCs. We assessed the immunogenicity of a lentiviral vector encoding the melanoma Ag NY-ESO-1 in HLA-A2 transgenic mice. Direct i.v. injection of NY-ESO-1 lentivirus induced NY-ESO-1(157-165)-specific CD8(+) cells, detected ex vivo with an A2/H-2K(b) chimeric class I tetramer. These NY-ESO-1(157-165)-specific CD8(+) cells could be expanded by boosting with an NY-ESO-1 vaccinia virus and could kill NY-ESO-1(157-165) peptide-pulsed targets in vivo. Such direct lentiviral vector injection was similar in potency to the injection of in vitro-transduced dendritic cells (DC). In addition, human monocyte-derived DC transduced by the NY-ESO-1 lentivirus stimulated an NY-ESO-1(157-165)-specific specific CTL clone. These data suggest that direct lentiviral transduction of DC in vivo might provide a powerful immunotherapeutic strategy.

摘要

慢病毒载体能够有效地转导多种非分裂细胞，包括抗原呈递细胞（APC）。我们在HLA - A2转基因小鼠中评估了编码黑色素瘤抗原NY - ESO - 1的慢病毒载体的免疫原性。通过静脉直接注射NY - ESO - 1慢病毒诱导出NY - ESO - 1（157 - 165）特异性CD8（+）细胞，利用A2/H - 2K（b）嵌合I类四聚体在体外进行检测。这些NY - ESO - 1（157 - 165）特异性CD8（+）细胞可以通过用NY - ESO - 1痘苗病毒加强免疫来扩增，并且能够在体内杀伤NY - ESO - 1（157 - 165）肽脉冲处理的靶细胞。这种直接注射慢病毒载体的效力与注射体外转导的树突状细胞（DC）相似。此外，由NY - ESO - 1慢病毒转导的人单核细胞衍生的DC刺激了NY - ESO - 1（157 - 165）特异性CTL克隆。这些数据表明，在体内对DC进行直接慢病毒转导可能提供一种强大的免疫治疗策略。