Generation of T-cell immunity to a murine melanoma using MART-1-engineered dendritic cells.
Generation of T-cell immunity to a murine melanoma using MART-1-engineered dendritic cells.
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使用 MART-1 工程树突状细胞产生针对小鼠黑色素瘤的 T 细胞免疫。
DOI：
10.1097/00002371-200001000-00008
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Economou,JS
中科院分区：
文献类型：
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作者：
Ribas,A;Butterfield,LH;Hu,B;Dissette,VB;Chen,AY;Koh,A;Amarnani,SN;Glaspy,JA;McBride,WH;Economou,JS
鼠黑素瘤B16表达人MART-1/Melan-A（MART-1）抗原的鼠对应物，具有68.6%的氨基酸序列同一性。在这项研究中，小鼠接种骨髓来源的小鼠树突状细胞基因修饰的复制缺陷型腺病毒载体表达人MART-1基因（AdVMART 1）。这种治疗产生了对未修饰的鼠B16黑色素瘤细胞的致死性肿瘤攻击的保护性应答。该反应由MART-1抗原特异性的主要组织相容性复合物I类限制性细胞毒性T淋巴细胞介导，当在体外再次暴露于MART-1时，产生高水平的干扰素-γ，并以钙依赖性机制裂解靶点，提示穿孔素/颗粒酶B裂解。MART-1由用于疫苗接种的树突状细胞呈递，而不是由宿主抗原呈递细胞交叉呈递的表位呈递。总之，经遗传修饰以表达人MART-1抗原的树突状细胞对B16黑色素瘤产生有效的鼠MART-1特异性保护性应答。
The murine melanoma B16 expresses the murine counterpart of the human MART-1/Melan-A (MART-1) antigen, sharing a 68.6% amino acid sequence identity. In this study, mice were vaccinated with bone marrow–derived murine dendritic cells genetically modified with a replication-incompetent adenoviral vector to express the human MART-1 gene (AdVMART1). This treatment generated a protective response to a lethal tumor challenge of unmodified murine B16 melanoma cells. The response was mediated by major histocompatibility complex class I–restricted cytotoxic T lymphocytes specific for MART-1 antigen, which produced high levels of interferon-γ when reexposed to MART-1 in vitro and lysed targets in a calcium-dependent mechanism suggestive of perforin/granzyme B lysis. MART-1 was presented by the dendritic cells used for vaccination and not by epitopes cross-presented by host antigen-presenting cells. In conclusion, dendritic cells genetically modified to express the human MART-1 antigen generate potent murine MART-1–specific protective responses to B16 melanoma.