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Effect of Size on Solid Tumor Disposition of Protein Therapeutics.

Drug Metab Dispos. 2019; 
Li Zhe,Li Yingyi,Chang Hsuan-Ping,Chang Hsueh-Yuan,Guo Leiming,Shah Dhav
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Nucleic Acid Purification & Analysis . The DNA sequenceof FcRn-nonbinding trastuzumab was synthesized by Genscript and clonedinto expression vector pcDNA5_FRT (Life Technologies, Carlsbad, CA). Get A Quote

摘要

In this study, we evaluated the effect of size on tumor disposition of protein therapeutics, including the plasma and tumor pharmacokinetics (PK) of trastuzumab (∼150 kDa), FcRn-nonbinding trastuzumab (∼150 kDa), F(ab) fragment of trastuzumab (∼100 kDa), Fab fragment of trastuzumab (∼50 kDa), and trastuzumab scFv (∼27 kDa) in both antigen (i.e., HER2)-overexpressing (N87) and antigen-nonexpressing (MDA-MB-468) tumor-bearing mice. The observed data were used to develop the maximum tumor uptake versus molecular weight and tumor-to-plasma area under the curve (AUC) ratio versus molecular weight relationships. Comparison of the PK of different sizes of FcRn nonbinding molecules in target-exp... More

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