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一种识别表皮生长因子受体(EGFR)和CD3的双特异性抗体诱导肿瘤细胞裂解

Induction of tumour cell lysis by a bispecific antibody recognising epidermal growth factor receptor (EGFR) and CD3.

作者信息

Knuth A, Bernhard H, Jäger E, Wölfel T, Karbach J, Jäggle C, Strittmatter W, Meyer zum Büschenfelde K H

机构信息

II Medizinische Klinik, Hämatologie/Onkologie, Krankenhaus Nordwest, Frankfurt a. Main, Germany.

出版信息

Eur J Cancer. 1994;30A(8):1103-7. doi: 10.1016/0959-8049(94)90466-9.

Abstract

A bispecific antibody construct (bAb) recognising CD3 and epidermal growth factor receptor (EGFR) was studied in vitro. Human peripheral blood lymphocytes (PBL), pre-activated with monoclonal antibody OKT-3 or with irradiated tumour cells, were armed with the bAb construct and targeted to autologous and allogeneic tumour target cells in culture. bAb EGFR x CD3 promoted significant cytolysis even at a concentration of 1 ng/ml. The specificity of target cell lysis was provided by the EGFR specificity of the bAb, as tumour cells negative for EGFR were not lysed. However, not only EGFR-positive tumour cells but also EGFR-positive normal cells were killed. Human renal cancer cell lines and the normal autologous kidney cell cultures expressing the same level of EGFR molecules were lysed to a similar extent. These results may contribute toward the planning of future clinical trials with such bAb.

摘要

在体外研究了一种识别CD3和表皮生长因子受体(EGFR)的双特异性抗体构建体(bAb)。用单克隆抗体OKT-3或经辐照的肿瘤细胞预激活的人外周血淋巴细胞(PBL),用bAb构建体武装,并靶向培养中的自体和同种异体肿瘤靶细胞。即使在浓度为1 ng/ml时,bAb EGFR x CD3也能促进显著的细胞溶解。靶细胞裂解的特异性由bAb的EGFR特异性提供,因为EGFR阴性的肿瘤细胞未被裂解。然而,不仅EGFR阳性肿瘤细胞,而且EGFR阳性正常细胞也被杀死。表达相同水平EGFR分子的人肾癌细胞系和正常自体肾细胞培养物被裂解的程度相似。这些结果可能有助于此类bAb未来临床试验的规划。

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