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Cytotoxicity of cytokine-induced killer cells targeted by a bispecific antibody to gastric cancer cells

机译:双特异性抗体靶向细胞因子诱导的杀伤细胞对胃癌细胞的细胞毒性

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摘要

The aim of the present study was to investigate the cytotoxic activity of cytokine-induced killer (CIK) cells targeted by an epidermal growth factor receptor (EGFR)/CD3 bispecific antibody (BsAb) to the gastric cancer cell line SGC7901. A BsAb was constructed by chemically cross-linking a monoclonal antibody (McAb) against human CD3 with another McAb against human EGFR. An immunocytochemistry assay was performed to detect the expression of EGFR in SGC7901 cells. The cytotoxic activity of CIK cells targeted by the EGFR/CD3 BsAb was analyzed by the 51Cr release assay, Subsequently, a comparison of the cytotoxic activity between CIK cells targeted by EGFR/CD3 BsAb, CIK cells targeted by EGFR McAb or/and CD3 McAb and CIK cells was performed. The antineoplastic activity of the CIK cells directed using the EGFR/CD3 BsAb in vivo was analyzed by tumor growth and tumor reduction assays. The cell lysis rate of CIK cells targeted by the EGFR/CD3 BsAb was higher compared with those of CIK cells targeted by CD3 McAb only or by CD3 McAb and EGFR McAb. The lysis rates of the latter two groups were significantly higher than those of CIK cells targeted by EGFR McAb only and CIK cells (P<0.05). The mean tumor reduction using the administration of CIK cells directed by the EGFR/CD3 BsAb was higher than those of the other groups (P<0.05). The results indicate that the EGFR/CD3 BsAb is able to enhance the ability of CIK cells to bind to and kill gastric cancer cells in vitro and in vivo.
机译:本研究的目的是研究表皮生长因子受体(EGFR)/ CD3双特异性抗体(BsAb)对胃癌细胞SGC7901靶向的细胞因子诱导的杀伤(CIK)细胞的细胞毒活性。通过将针对人类CD3的单克隆抗体(McAb)与另一针对人类EGFR的McAb化学交联来构建BsAb。进行了免疫细胞化学分析以检测SGC7901细胞中EGFR的表达。用 51 Cr释放分析法分析了EGFR / CD3 BsAb靶向的CIK细胞的细胞毒活性,随后比较了EGFR / CD3 BsAb靶向的CIK细胞与靶向的CIK细胞之间的细胞毒活性。通过EGFR McAb或/和CD3 McAb和CIK细胞进行。通过肿瘤生长和肿瘤减少测定法分析了在体内使用EGFR / CD3 BsAb指导的CIK细胞的抗肿瘤活性。与仅通过CD3 McAb或通过CD3 McAb和EGFR McAb靶向的CIK细胞相比,由EGFR / CD3 BsAb靶向的CIK细胞的细胞裂解率更高。后两组的裂解率显着高于仅用EGFR McAb靶向的CIK细胞和CIK细胞(P <0.05)。使用由EGFR / CD3 BsAb指导的CIK细胞给药的平均肿瘤减少率高于其他组(P <0.05)。结果表明,EGFR / CD3 BsAb能够增强CIK细胞在体外和体内结合并杀死胃癌细胞的能力。

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