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1. 发明申请

WO2009034172A1 ENHANCING THE T-CELLS STIMULATORY CAPACITY OF HUMAN ANTIGEN PRESENTING CELLS AND THEIR USE IN VACCINATION 审中-公开
标题翻译：增强人类抗原呈递细胞的T细胞刺激能力及其在疫苗中的使用
公开(公告)号：WO2009034172A1
公开(公告)日：2009-03-19
申请号：PCT/EP2008/062174
申请日：2008-09-12
申请人： VRIJE UNIVERSITEIT BRUSSEL , THIELEMANS, Kris, Maria, Magdalena , BONEHILL, Aude
发明人： THIELEMANS, Kris, Maria, Magdalena , BONEHILL, Aude
IPC分类号： C12N5/06 , C12N5/08
CPC分类号： C12N5/0639 , C12N2501/22 , C12N2501/23 , C12N2501/52 , C12N2501/599 , Y02A50/386 , Y02A50/403 , Y02A50/407 , Y02A50/484
摘要： With the current invention, we provide new methods of enhancing the T-cell stimulatory capacity of human dendritic cells (DCs) and their use in cancer vaccination. The method comprises the introduction of different molecular adjuvants to human DCs through transfection with at least two mRNA or DNA molecules encoding markers selected from the group of: CD40L, CD70, constitutively active TLR4 (caTLR4), IL-12p70, EL-selectin, CCR7 and/or 4-1 BBL; or in combination with inhibition of SOCS, A20, PD-L1 and/or STAT3 expression, for example through siRNA transfection. We could show a clear increase in the immunostimulatory capacity of DCs obtained in this way, enabling them to elicit an unexpectedly high T-cell immune response in vitro. Introduction of at least two of the above molecules, in combination with a tumor-specific antigen enables the DCs to elicit a significant host-mediated T-cell immune response in vivo against the tumor antigen and thus makes them very attractive in the manufacturing of anti-cancer vaccines.
摘要翻译：利用本发明，我们提供增强人树突状细胞（DC）的T细胞刺激能力及其在癌症疫苗接种中的应用的新方法。该方法包括通过用编码选自以下组的标记的标记的至少两个mRNA或DNA分子进行转染而引入不同的分子佐剂：DC40，CD70，组成型活性TLR4（caTLR4），IL-12p70，EL-选择素，CCR7 和/或4-1BBL; 或与SOCS，A20，PD-L1和/或STAT3表达的抑制的组合，例如通过siRNA转染。我们可以显示出以这种方式获得的DC的免疫刺激能力的明显增加，使得它们能够在体外引起意想不到的高T细胞免疫应答。引入至少两种上述分子与肿瘤特异性抗原结合使得DC能够在体内引起显着的宿主介导的T细胞免疫反应，抵抗肿瘤抗原，因此使得它们在制备抗体中非常有吸引力 - 癌症疫苗。

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