TNF receptor II fusion protein with tandemly repeated Fc domains.
TNF receptor II fusion protein with tandemly repeated Fc domains.
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具有串联重复 Fc 结构域的 TNF 受体 II 融合蛋白。
DOI：
10.1093/jb/mvq149
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发表时间：
2011
影响因子：
2.7
通讯作者：
Y. Masuho
中科院分区：
文献类型：
--
作者：
H. Nagashima;Kaname Kaneko;Ayaka Yamanoi;Sotaro Motoi;S. Konakahara;J. Kohroki;Y. Masuho
与人IgG 1 Fc区融合的肿瘤坏死因子（TNF）受体II的胞外结构域（TNFRII-Fc）以及抗TNF抗体已用于治疗类风湿性关节炎。然而，TNFRII-Fc在针对细胞表面上携带TNF的细胞的抗体依赖性细胞毒性（ADCC）和补体依赖性细胞毒性（CDC）方面不如这些抗体有效。我们假设这些活性可以通过融合TNFRII与串联重复的Fc（TNFRII-Fc-Fc）来增加。TNFRII-Fc-Fc对可溶性TNF-α和跨膜TNF-α的亲和力和TNF-α细胞毒性抑制活性与TNFRII-Fc的亲和力和TNF-α细胞毒性抑制活性一样强。TNFRII-Fc-Fc对Fcγ受体的结合亲合力远高于TNFRII-Fc，并且在ADCC和CDC方面对表达跨膜TNF-α的细胞更有效。检测到80 kDa的TNFRII-Fc-Fc以及200 kDa的TNFRII-Fc-Fc。TNFRII-Fc-Fc（80 kDa）在ADCC和CDC方面与TNFRII-Fc一样有效。这些结果表明，受体-Fc融合蛋白的Fc多聚化可以增强效应子功能，如ADCC和CDC，从而具有提供上级治疗效果的潜力。不仅TNFRII-Fc如此，其他受体-Fc融合蛋白也是如此。
The extracellular domain of tumour necrosis factor (TNF) receptor II fused with the human IgG1 Fc region (TNFRII-Fc), as well as antibodies against TNF, has been used to treat rheumatoid arthritis. However, TNFRII-Fc is less effective than these antibodies in terms of antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against cells bearing TNF on the cell surface. We hypothesized that these activities could be increased by fusing TNFRII with tandemly repeated Fc (TNFRII-Fc-Fc). The affinities of TNFRII-Fc-Fc for soluble TNF-α and transmembrane TNF-α and the TNF-α cytotoxicity-inhibitory activity were as potent as those of TNFRII-Fc. TNFRII-Fc-Fc showed much higher binding avidity for Fcγ receptors than TNFRII-Fc and was more potent in terms of both ADCC and CDC against cells expressing transmembrane TNF-α. TNFRII-Fc-Fc of 80 kDa, as well as TNFRII-Fc-Fc of 200 kDa, was detected. TNFRII-Fc-Fc (80 kDa) was as potent as TNFRII-Fc in terms of both ADCC and CDC. These results suggest that Fc multimerization of receptor-Fc fusion proteins can augment effector functions such as ADCC and CDC, and thereby have the potential to provide a superior therapeutic effect. This may be the case not only for TNFRII-Fc but also for other receptor-Fc fusion proteins.
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影响因子：
45.3
作者：
Weng, WK;Levy, R
通讯作者：
Levy, R
影响因子：
20.3
作者：
Byrd, JC;Kitada, S;Reed, JC
通讯作者：
Reed, JC
影响因子：
20.3
作者：
Bowles, Julie A.;Wang, Siao-Yi;Weiner, George J.
通讯作者：
Weiner, George J.
单体人 IgG 的结合定义了大颗粒淋巴细胞/自然杀伤细胞上 Fc gamma RIII 的表达多态性。
DOI：
--
发表时间：
1993
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Vance,BA;Huizinga,TW;Wardwell,K;Guyre,PM
通讯作者：
Guyre,PM