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    • 2. 发明公开
    • ENHANCING THE T-CELLS STIMULATORY CAPACITY OF HUMAN ANTIGEN PRESENTING CELLS AND THEIR USE IN VACCINATION
    • 改善与人抗原及其USE IN接种细胞的T细胞刺激能力
    • EP3173474A1
    • 2017-05-31
    • EP16159782.8
    • 2008-09-12
    • VRIJE UNIVERSITEIT BRUSSEL
    • Thielemans, KrisBonnehill, Aude
    • C12N5/0784
    • C12N5/0639C12N2501/22C12N2501/2307C12N2501/52C12N2501/599C12N2510/00Y02A50/386Y02A50/403Y02A50/407Y02A50/484
    • 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.
    • 与当前的发明中,我们提供增强的人树突状细胞(DC)和它们在癌症疫苗使用的T细胞刺激能力的新方法。 该方法包括引入不同的分子佐剂以人DC的通过转染从以下组中选择的至少两种mRNA或编码标记物的DNA分子:CD40L,CD70,组成性活性TLR4(caTLR4),IL-12p70的,EL选择蛋白,CCR7 和/或4-1 BBL; 或与SOCS,A20,PD-L1和/或抑制STAT3的表达,例如,通过转染组合。 我们可以显示出以这种方式获得DC的免疫刺激能力明显增加,使他们在体外出乎意料的高T细胞免疫反应引起。 至少两个以上的分子,介绍并结合肿瘤特异性抗原启用的DCs引起在针对肿瘤抗原体内显著宿主介导的T-细胞免疫应答,从而使得它们在制造抗非常有吸引力的 -cancer疫苗。