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目的 :研究应用抗HER 2抗原和CD3抗原的双向基因工程抗体BsAbHER 2×CD3介导T淋巴细胞对过度表达HER 2乳腺癌细胞的细胞毒作用。方法 :以过度表达HER 2的乳腺癌细胞株SK BR 3为靶细胞 ,T淋巴细胞为效应细胞 ,采用MTT法、3 H TdR掺入法测定BsAbHER 2×CD3对靶细胞、效应细胞的抑制作用及其介导的效应细胞对靶细胞的杀伤作用。结果 :BsAbHER 2×CD3具有MAbHER 2和MAbCD3的双重特性 ,既能抑制SK BR 3细胞生长 ,又可促进正常人外周血T淋巴细胞增殖。BsAbHER 2×CD3介导T淋巴细胞对靶细胞产生显著的细胞毒作用 ,明显强于MAbHER 2对靶细胞的作用 ,E∶T =2 0∶1为最佳效靶比。结论 :BsAbHER 2×CD3 ,既可以与HER 2过度表达的肿瘤细胞特异性结合 ,又可以介导T淋巴细胞对肿瘤细胞产生特异性杀伤作用 ,具有明显的抗肿瘤作用
OBJECTIVE: To study the cytotoxic effect of T lymphocytes on HER2-overexpressing breast cancer cells using bi-directional genetically engineered antibody BsAbHER2 × CD3 against HER2 antigen and CD3 antigen. Methods: The breast cancer cell line SK BR 3 overexpressing HER 2 was used as target cells and T lymphocytes as effector cells. The inhibitory effect of BsAbHER 2 × CD3 on target cells and effector cells was determined by MTT method and 3 H TdR incorporation assay And its effect of killing effector cells on target cells. Results: BsAbHER 2 × CD3 has the dual characteristics of MAbHER 2 and MAbCD3, which can not only inhibit the growth of SK BR 3 cells but also promote the proliferation of normal human peripheral blood T lymphocytes. BsAbHER 2 × CD3-mediated T lymphocytes produced significant cytotoxicity on target cells, which was significantly stronger than that of MAbHER 2 on target cells. E: T = 20: 1 was the best target ratio. CONCLUSION: BsAbHER 2 × CD3 can specifically bind to tumor cells overexpressing HER 2, mediate the specific cytotoxic effect of T lymphocytes on tumor cells, and have obvious antitumor effects