Transferrin-antibody fusion proteins are effective in brain targeting.
Transferrin-antibody fusion proteins are effective in brain targeting.
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转铁蛋白-抗体融合蛋白可有效地靶向大脑。
DOI：
10.1073/pnas.92.7.2820
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发表时间：
1995
影响因子：
11.1
通讯作者：
Morrison,SL
中科院分区：
文献类型：
--
作者：
Shin,SU;Friden,P;Moran,M;Olson,T;Kang,YS;Pardridge,WM;Morrison,SL
在本研究中，转铁蛋白（Tf）的受体结合电位与抗体结合特异性相关联。人Tf在三个位置与小鼠-人嵌合IgG3融合：重链常数区1 （CH1）末端、铰链后和CH3后。得到的Tf抗体融合蛋白能够结合抗原和Tf受体。CH3-Tf融合蛋白没有补体介导的细胞溶解作用，但具有IgG受体I （Fc γ RI）结合活性。最重要的是，所有的融合蛋白都被脑实质吸收，其中0.3%的注射剂量的hinge-Tf融合蛋白迅速靶向到大脑。从脑实质中恢复的碘化CH3-Tf融合蛋白表明融合蛋白可以完整地穿过血脑屏障。这些融合蛋白的结合特异性可用于脑递送非共价结合的配体，如药物和肽，或靶向存在于脑内的抗原。
In the present study, the receptor binding potential of transferrin (Tf) was linked to an antibody binding specificity. Human Tf was fused to mouse-human chimeric IgG3 at three positions: at the end of heavy chain constant region 1 (CH1), after the hinge, and after CH3. The resulting Tf-antibody fusion proteins were able to bind antigen and the Tf receptor. The CH3-Tf fusion protein showed no complement-mediated cytolysis but possessed IgG receptor I (Fc gamma RI) binding activity. Most importantly, all of the fusion proteins demonstrated significant uptake into brain parenchyma, with 0.3% of the injected dose of the hinge-Tf fusion protein rapidly targeted to the brain. Recovery of iodinated CH3-Tf fusion protein from the brain parenchyma demonstrated that the fusion proteins can cross the blood-brain barrier intact. The binding specificity of these fusion proteins can be used for brain delivery of noncovalently bound ligands, such as drugs and peptides, or for targeting antigens present within the brain.