Specific tissue factor delivery using a tumor-homing peptide for inducing tumor infarction

Biochemical Pharmacology
Quanwei ShiSuping Li

Abstract

Targeting the human blood coagulation-inducing protein tissue factor (TF) to the tumor vasculature to induce infarction and disrupt the blood vessels has proven to be an effective approach for tumor therapy. In this study, we investigated the thrombogenic activity and anti-tumor potential of a novel fusion protein (tTF-CREKA) comprising the extracellular domain of human tissue factor (truncated TF, tTF) and a tumor targeting pentapeptide, Cys-Arg-Glu-Lys-Ala (CREKA). tTF is soluble and inactive in its free state, but when it is targeted to the plasma membrane of both tumor vessel endothelial cells and stromal cells by the CREKA peptide, its native coagulation-inducing activity is restored. Systemic administration of the tTF-CREKA fusion protein into tumor-bearing mice induced tumor-selective intravascular thrombosis and reduced tumor blood perfusion, consequently inhibiting tumor growth. The development of tTF-CREKA introduces a new method for treating a wide spectrum of solid tumors by selectively blocking tumor blood supply.

Citations

Dec 20, 2019·Artificial Cells, Nanomedicine, and Biotechnology·Mingyuan ZouJianghua Yan
Jul 3, 2021·Cancers·Andrew F BerdelTorsten Kessler
Jul 17, 2021·Acta Biomaterialia·Ying Zhang, Jingni He
Aug 21, 2019·Bioconjugate Chemistry·Marzieh GeranpayehvagheiGuangjun Nie
Aug 23, 2019·Accounts of Chemical Research·Zifu LiGuangjun Nie
Feb 4, 2021·ACS Central Science·Brianna M VickermanDavid S Lawrence

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