Generation of chimeric bispecific G250/anti-CD3 monoclonal antibody, a tool to combat renal cell carcinoma.
Generation of chimeric bispecific G250/anti-CD3 monoclonal antibody, a tool to combat renal cell carcinoma.
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DOI：
10.1038/bjc.1996.430
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发表时间：
1996-09
影响因子：
8.8
通讯作者：
Litvinov, S V
中科院分区：
文献类型：
--
作者：
Luiten, R M;Coney, L R;Fleuren, G J;Warnaar, S O;Litvinov, S V
单克隆抗体（MAb） G250结合在肾细胞癌（RCC）中表达的肿瘤相关抗原，已被证明是抗体介导的免疫治疗的合适靶点。一种同时具有G250和抗cd3特异性的双特异性抗体可以将表达G250抗原的RCC靶细胞与T细胞交联，并介导这些靶细胞的裂解。使用小鼠抗体的治疗研究受到对注射抗体的免疫反应（HAMA反应）的限制，这种反应可以通过使用嵌合抗体来降低。我们将G250单抗和抗CD3单抗的重链和轻链嵌合基因转染到骨髓瘤细胞系中，获得了G250/抗CD3单抗的嵌合双特异性。细胞毒性实验显示，嵌合双特异性单抗能够介导克隆的人CD8+T细胞或il -2刺激的外周血淋巴细胞（PBLs）裂解RCC细胞系。单抗介导的裂解对表达G250抗原的靶细胞具有特异性，并且在低至0.01微克ml-1的浓度下有效。该嵌合双特异性G250/抗cd3单抗可能是目前使用的基于il -2的晚期肾细胞癌治疗的有效辅助。
The monoclonal antibody (MAb) G250 binds to a tumour-associated antigen, expressed in renal cell carcinoma (RCC), which has been demonstrated to be a suitable target for antibody-mediated immunotherapy. A bispecific antibody having both G250 and anti-CD3 specificity can cross-link G250 antigen-expressing RCC target cells with T cells and can mediate lysis of such targets. Therapy studies with murine antibodies are limited by immune responses to the antibodies injected (HAMA response), which can be decreased by using chimeric antibodies. We generated a chimeric bispecific G250/anti CD3 MAb by transfecting chimeric genes of heavy and light chains for both the G250 MAb and the anti-CD3 MAb into a myeloma cell line. Cytotoxicity assays revealed that the chimeric bispecific MAb was capable of mediating lysis of RCC cell lines by cloned human CD8+T cells or by IL-2-stimulated peripheral blood lymphocytes (PBLs). Lysis mediated by the MAb was specific for target cells that expressed the G250 antigen and was effective at concentrations as low as 0.01 microgram ml-1. The chimeric bispecific G250/anti-CD3 MAb produced may be an effective adjuvant to the currently used IL-2-based therapy of advanced renal cell arcinoma.