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    • 1. 发明申请
    • RAPID ONE-STEP METHOD FOR GENERATION OF ANTIGEN LOADED DENDRITIC CELL VACCINE FROM PRECURSORS
    • 用于从前体产生抗原负载的细胞真菌的快速一步法
    • WO2004050855A2
    • 2004-06-17
    • PCT/US2003/038553
    • 2003-12-04
    • BAYLOR RESEARCH INSTITUTEBANCHEREAU, Jacques, F.PALUCKA, Anna, K.
    • BANCHEREAU, Jacques, F.PALUCKA, Anna, K.
    • C12N
    • A61K39/0011A61K2039/5152A61K2039/5154C12N5/0639C12N2501/22C12N2501/25
    • A one-step method for producing antigen loaded antigen-presenting cells from monocytes ex vivo has been found which comprises contacting the monocytes with a composition comprising an activator such as TNF alpha preferably in combination with at least one growth factor such as GM-CSF and at least one soluble or particulate antigen. According to the methods of the present invention, antigen-loaded dendritic cell vaccines can be generated within as little as three (3) days. In another method of the present invention, antigen loaded antigen-presenting cells are produced from monocytes ex vivo by contacting the monocytes with TNF alpha and granulocyte-macrophage colony stimulating factor at one time point to form antigen-presenting cells and then contacting antigen­presenting cells with soluble or particulate antigenic material at a second time point to form antigen loaded antigen-presenting cells, wherein the antigen loaded antigen-presenting cells are produced in less than four days. The present invention also includes a vaccine which comprises monocyte-derived antigen loaded antigen-presenting cells, wherein the antigen­presenting cells are composed of two or more subsets selected from the group consisting of Langerhans cells with surface markers (CD 1 a+ CD207+); interstitial dendritic cells with surface markers (CD 1a+ CD207-); double negative dendritic cells with surface markers 20 (CD 1 a-CD 14-); and dendritic cells with surface markers (CD 14+ CD 1 a- CD209+).
    • 已经发现从体外从单核细胞产生抗原负载抗原呈递细胞的一步法包括使单核细胞与包含活化剂如TNFα的组合物接触,优选与至少一种生长因子如GM-CSF和 至少一种可溶或微粒抗原。 根据本发明的方法,可以在短短三(3)天内产生抗原负载的树突状细胞疫苗。 在本发明的另一种方法中,抗原呈递细胞由单核细胞通过单核细胞与TNFα和粒细胞 - 巨噬细胞集落刺激因子在一个时间点接触形成抗原呈递细胞,然后将抗原呈递细胞与 可溶性或微粒状抗原物质,以形成抗原负载的抗原呈递细胞,其中抗原呈递细胞在不到四天内产生。 本发明还包括一种疫苗,其包含单核细胞衍生的抗原负载抗原呈递细胞,其中所述抗原呈递细胞由两个或更多个选自具有表面标记的朗格汉斯细胞(CD1a + CD207 +)的子集组成; 具有表面标志物的间质树突状细胞(CD 1a + CD207-); 具有表面标记20的双负性树突状细胞(CD 1 a-CD 14-); 和具有表面标志物的树突状细胞(CD14 + CD11a-CD209 +)。