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IgG Fc engineering to modulate antiboc affector functions 被引量:18
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作者 Xinhua Wang Mary Mathieu Randall J. Brezski 《Protein & Cell》 SCIE CAS CSCD 2018年第1期63-73,共11页
Therapeutic monoclonal antibodies are among the most effective biotherapeutics to date. An important aspect of antibodies is their ability to bind antigen while at the same time recruit immune effector functions. The ... Therapeutic monoclonal antibodies are among the most effective biotherapeutics to date. An important aspect of antibodies is their ability to bind antigen while at the same time recruit immune effector functions. The majority of approved recombinant monoclonal antibody therapies are of the human IgG1 subclass, which can engage both humoral and cellular components of the immune system. The wealth of information generated about antibodies has afforded investigators the ability to molecularly engineer antibodies to modulate effector functions. Here, we review various antibody engineering efforts intended to improve efficacy and safety relative to the human IgG isotype. Further, we will discuss pro- posed mechanisms by which engineering approaches led to modified interactions with immune components and provide examples of clinical studies using next generation antibodies. 展开更多
关键词 antibody-dependent cell-mediated cytotoxicity antibody-dependent cellular phagocytosis complement-dependent cytotoxicity Fc engineering fcgamma receptor monoclonal antibody neonatal Fc receptor
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FcγRIIb基因修饰树突状细胞对大鼠原位肝移植排斥反应的影响
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作者 李立强 张武 +3 位作者 李志文 闫文涛 焦龙杏 李明皓 《中华普通外科杂志》 CSCD 北大核心 2021年第2期132-136,共5页
目的研究FcγRIIb基因修饰树突状细胞对大鼠原位肝移植术后肝功能及病理排斥反应的影响。方法利用基因克隆技术构建含Lewis大鼠FcγRIIb基因的重组慢病毒表达载体TRE-FcγRIIb。分别包装TRE-FcγRIIb表达病毒与TET-on可诱导病毒,用其共... 目的研究FcγRIIb基因修饰树突状细胞对大鼠原位肝移植术后肝功能及病理排斥反应的影响。方法利用基因克隆技术构建含Lewis大鼠FcγRIIb基因的重组慢病毒表达载体TRE-FcγRIIb。分别包装TRE-FcγRIIb表达病毒与TET-on可诱导病毒,用其共感染DA大鼠骨髓来源未成熟树突状细胞并检测FcγRIIb的表达。将供体DA大鼠与受体Lewis大鼠按照体重进行配对后随机分为三组,三组均行DA-Lewis的大鼠原位肝移植术。对照组(A组)不给予任何预处理。环孢素A组(B组)术后第2天开始给予环孢素A处理。FcγRIIb基因修饰未成熟树突状细胞组(C组)术前1d供体大鼠静脉注射FcγRIIb修饰的DA大鼠骨髓来源的未成熟树突状细胞(1×10^(6)细胞)。术后第7天分别取血和肝脏检测肝功能和肝脏病理变化。结果C组术后第7天肝功能异常明显低于对照组(P<0.05);C组术后第7天肝脏病理排斥反应明显低于对照组(P<0.05)。对照组中的大鼠平均存活天数为12.8d;B组的大鼠平均存活天数为65.3d;C组的大鼠平均存活天数为58.5d。结论FcγRIIb基因修饰未成熟树突状细胞可以降低大鼠原位肝移植术后肝功能异常,减轻术后大鼠肝脏急性排斥反应。 展开更多
关键词 肝移植 移植物排斥 FCΓRIIB 未成熟树突状细胞
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