T-cell retargeting using bispecific monoclonal antibodies in a rat colon carcinoma model. I. Significant bispecific lysis of syngeneic colon carcinoma CC531 is critically dependent on prolonged preactivation of effector T-lymphocytes by immobilized anti-T-cell receptor antibody.

G D Beun, D H van Eendenburg, W E Corver, C J van de Velde, G J Fleuren
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引用次数: 20

Abstract

In order to develop a rat model that reflects human weakly or nonimmunogenic tumor-host relationships and allows investigation of T-cell retargeting with bispecific monoclonal antibodies in vivo, we prepared several mixed hybridomas. One fusion partner was the anti-rat-T-cell receptor (TCR)-framework hybridoma R73 and the others were hybridomas producing antibodies against CC531, a Wag rat colon carcinoma. Stimulation of Wag rat spleen cells with immobilized R73 mAb and rIL-2 yielded predominantly CD8 positive effector T-lymphocytes, which lysed control P815 target cells efficiently in R73-mediated reverse antibody-dependent cellular cytotoxicity (ADCC). The capacity of these effectors to cause significant hybrid antibody-mediated lysis of CC531 emerged several days later, was critically dependent on prolonged stimulation with immobilized R73, and was associated with increased N-alfa-benzyloxycarbonyl-L-lysine thiobenzyl esterase content.

使用双特异性单克隆抗体在大鼠结肠癌模型中的t细胞重靶向。1 .同基因结肠癌CC531的显著双特异性裂解严重依赖于固定化抗t细胞受体抗体对效应t淋巴细胞的长时间预激活。
为了建立反映人类弱或非免疫原性肿瘤-宿主关系的大鼠模型,并允许研究体内双特异性单克隆抗体的t细胞重靶向,我们制备了几种混合杂交瘤。一个融合伙伴是抗大鼠t细胞受体(TCR)框架杂交瘤R73,其他的是产生抗CC531抗体的杂交瘤,CC531是Wag大鼠结肠癌。用固定的R73单抗和rIL-2刺激Wag鼠脾细胞,产生主要的CD8阳性效应t淋巴细胞,在R73介导的反向抗体依赖性细胞毒性(ADCC)中有效地裂解对照P815靶细胞。几天后,这些效应物引起杂交抗体介导的CC531裂解的能力出现,严重依赖于固定R73的长时间刺激,并与n - α -苄氧羰基-l -赖氨酸硫苯酯酶含量增加有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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