Dendritic cells genetically modified with an adenovirus vector encoding the cDNA for a model antigen induce protective and therapeutic antitumor immunity.
Dendritic cells genetically modified with an adenovirus vector encoding the cDNA for a model antigen induce protective and therapeutic antitumor immunity.
复制标题
树突状细胞用编码cDNA的腺病毒载体基因修饰的模型抗原诱导保护性和治疗性抗肿瘤免疫。
DOI：
10.1084/jem.186.8.1247
复制
发表时间：
1997-10-20
期刊：
影响因子：
--
通讯作者：
Crystal RG
中科院分区：
文献类型：
--
作者：
Song W;Kong HL;Carpenter H;Torii H;Granstein R;Rafii S;Moore MA;Crystal RG
树突状细胞（Dendritic cells，DC）是一种强有力的抗原提呈细胞，在抗肿瘤免疫应答的启动中起重要作用。在这项研究中，我们表明，通过使用复制缺陷型重组腺病毒载体，可以对小鼠表皮来源的DC系和原代骨髓来源的DC进行基因修饰以表达模型抗原β-半乳糖苷酶（βgal），并且修饰的DC能够引发抗原特异性的MHC限制性CTL应答。重要的是，使用具有表达βgal的同基因结肠癌细胞的鼠转移性肺肿瘤模型，我们表明用遗传修饰的DC系或骨髓DC免疫小鼠赋予针对致死性肿瘤攻击的有效保护，以及对预先建立的肿瘤的抑制，导致显著的存活优势。我们的结论是，基因修饰的DC表达抗原，也表达在肿瘤中可以导致抗原特异性，抗肿瘤杀伤细胞，伴随着对肿瘤的挑战和现有肿瘤的大小减少的阻力。
Dendritic cells (DCs) are potent antigen-presenting cells that play a critical role in the initiation of antitumor immune responses. In this study, we show that genetic modifications of a murine epidermis-derived DC line and primary bone marrow–derived DCs to express a model antigen β-galactosidase (βgal) can be achieved through the use of a replication-deficient, recombinant adenovirus vector, and that the modified DCs are capable of eliciting antigen-specific, MHC-restricted CTL responses. Importantly, using a murine metastatic lung tumor model with syngeneic colon carcinoma cells expressing βgal, we show that immunization of mice with the genetically modified DC line or bone marrow DCs confers potent protection against a lethal tumor challenge, as well as suppression of preestablished tumors, resulting in a significant survival advantage. We conclude that genetic modification of DCs to express antigens that are also expressed in tumors can lead to antigen-specific, antitumor killer cells, with a concomitant resistance to tumor challenge and a decrease in the size of existing tumors.