摘要: |
自1989年抑制HIV-1感染的CD4-Fc融合蛋白被首次报道以来,Fc融合蛋白的治疗性应用在医药学领域引起广泛关注。Fc融合蛋白由功能分子和免疫球蛋白的Fc结构域组成,不仅具有蛋白的生物学功能且兼具抗体的特性,如在体内具有长半衰期、诱导抗体依赖细胞介导的细胞毒性效应(antibody-dependent cell-mediated cytotoxicity,ADCC)等。通过对Fc结构域进行糖基化、脱酰胺化、氨基酸定点突变改造,还可增强或减弱其介导的ADCC等效应,用于临床疾病的诊断与治疗。另外,Fc融合蛋白在多个非临床领域也有广泛应用。本文对重组Fc融合蛋白的结构特征和药理学特性、临床药物开发及其在非临床领域中的应用与发展进行综述。 |
关键词: Fc融合蛋白 临床应用 分子设计 免疫球蛋白 |
DOI:10.12025/j.issn.1008-6358.2022.20210113 |
分类号: |
基金项目:国家自然科学基金(81671989),上海市科技创新计划项目(18411951300). |
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Research progress of recombinant Fc fusion protein drugs |
SUN Yu-fang1, ZONG Hui1, GUO Shi-yu1, CHEN Si-min1, AN Mao-mao1, SHEN Hui2
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1.Department of Pharmacy, Tenth People's Hospital Affiliated to Tongji University, Shanghai 200072, China;2.Department of Laboratory Medicine, Southern Branch, Dongfang Hospital, Tongji University, Shanghai 200120, China
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Abstract: |
Since the first report of CD4-Fc fusion protein in 1989, Fc fusion protein has received increased attention in the medical field with its therapeutic potential. Fc fusion protein consists of the immunoglobin Fc domain and fused partners, which has both biological functions of fused partners and characteristic of antibody, showing significantly improved stability and specificity in vivo. Antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) mediated by Fc fusion protein can be increased or decreased by glycosylation, deamidation, and site-directed amino acid modification of the Fc domain, which has been widely used in clinical diagnosis and treatment, and also in nonclinical applications. This review summarize the structural and pharmacological properties of Fc fusion protein and discuss its future development directions in clinical and nonclinical fields. |
Key words: Fc fusion protein clinical applications molecular design immunoglobulins |