首页> 外文期刊>Clinical immunology: The official journal of the Clinical Immunology Society >Cytokine-induced killer (CIK) cells bound with anti-CD3/anti-CD133 bispecific antibodies target CD133high cancer stem cells in vitro and in vivo
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Cytokine-induced killer (CIK) cells bound with anti-CD3/anti-CD133 bispecific antibodies target CD133high cancer stem cells in vitro and in vivo

机译:与抗CD3 /抗CD133双特异性抗体结合的细胞因子诱导的杀伤(CIK)细胞在体外和体内靶向CD133高癌干细胞

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摘要

CD133 is a common marker of cancer stem cells (CSCs). We generated an anti-CD3/anti-CD133 bispecific antibody (BsAb) and bound it to the cytokine-induced killer (CIK) cells as effector cells (BsAb-CIK) to target CD133high CSCs. The killing of CD133high pancreatic (SW1990) and hepatic (Hep3B) cancer cells by the BsAb-CIK cells was significantly (p0.05) higher than the killing by the parental CIK or by CIK cells bound with anti-CD3 (CD3-CIK) without CD133 targeting. In nude mice, the BsAb-CIK cells inhibited CD133high tumor growth significantly (p0.05) more than that by CIK or CD3-CIK cells, or by the BsAb alone. BsAb-CIK cells co-cultured with CD133high cells produced significantly (p0.05) higher amount of IFN-γ. Treatment with the BsAb-CIK cells significantly downregulated the expression of S100P and IL-18bp, but upregulated STAT1. The findings may help with the development of novel immunotherapies for patients with cancer containing CD133high CSCs by selectively targeting this cell population.
机译:CD133是癌症干细胞(CSC)的常见标记。我们生成了抗CD3 /抗CD133双特异性抗体(BsAb),并将其与作为效应细胞(BsAb-CIK)的细胞因子诱导的杀伤(CIK)细胞结合,以靶向CD133高CSC。 BsAb-CIK细胞对CD133高胰腺(SW1990)和肝(Hep3B)癌细胞的杀伤作用比亲本CIK或与抗CD3结合的CIK细胞(CD3-CIK)的杀伤作用显着(p <0.05)高没有CD133定位。在裸鼠中,BsAb-CIK细胞对CD133high肿瘤生长的抑制作用比CIK或CD3-CIK细胞或单独的BsAb抑制作用显着(p <0.05)。与CD133high细胞共培养的BsAb-CIK细胞产生的IFN-γ量明显更高(p <0.05)。 BsAb-CIK细胞处理显着下调S100P和IL-18bp的表达,但上调STAT1。通过选择性靶向该细胞群,该发现可能有助于开发针对包含CD133高CSC的癌症患者的新型免疫疗法。

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