Generation of a potent recombinant homophilic chimeric anti-CD20 antibody.

Generation of a potent recombinant homophilic chimeric anti-CD20 antibody.
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产生有效的重组同亲嵌合抗 CD20 抗体。

DOI:
10.1089/hyb.2012.0073
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发表时间:
2012
期刊:
Hybridoma (2005)
影响因子:
--
通讯作者:
Amick,Jean
Amick,Jean
中科院分区:
--
文献类型:
--
作者:
Kohler,Heinz;Rector,Kyle;Amick,Jean

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以前,我们通过化学偶联一个亲同性肽到抗体上,提高了治疗性抗体在靶向、诱导细胞凋亡和体外生长抑制方面的效力。在这里,我们描述了一个嵌合融合基因的构建,该基因来源于小鼠抗cd20抗体(1F5)可变区,在人类IgG1序列的c端具有一个工程的亲同源结构域。构建体在CHO悬浮细胞中表达并纯化。将亲性抗cd20抗体的效价与不含工程亲性结构域的嵌合抗体进行比较。在这个比较中,亲同型抗CD20抗体显示与人CD20细胞系的结合增加,并且在三种细胞系中显著增加ADCC, CDC和诱导凋亡。此外,亲同型抗cd20抗体对两种细胞系的增殖抑制作用增强。这些数据表明,具有增强治疗效力的亲同性融合蛋白抗体可以用工业标准的发酵方案生产。
Previously we increased the potency of therapeutic antibodies in targeting, induction of apoptosis, and growth inhibitionin vitroandin vivoby chemically conjugating a homophilic peptide to the antibody. Here, we describe the construction of a chimeric fusion gene derived from the murine anti-CD20 antibody (1F5) variable region, with an engineered homophilic domain at the C-terminus of the human IgG1 sequence. The construct was expressed in CHO suspension cells and purified. The potency of the homophilic anti-CD20 antibody was compared to a chimeric antibody without the engineered homophilic domain. In this comparison, the homophilic anti-CD20 antibody showed increased binding to a human CD20 cell line, and significantly more ADCC, CDC, and induction of apoptosis in three cell lines. In addition, the homophilic anti-CD20 antibody demonstrated increased inhibition of proliferation of two cell lines. These data show that homophilic fusion protein antibodies with enhanced therapeutic potency can be produced with industry-standard fermentation protocols.
在静止的 Swiss 3T3 细胞中,蛋白激酶 C 的激活可快速引发离子反应。
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