Intramuscular Expression of Plasmid-Encoded FVII-Fc Immunoconjugate for Tumor Immunotherapy by Targeting Tumoral Blood Vessels and Cells

摘要: Tissue factor (TF) has been confirmed to be specifically expressed by vascular endothelial cells (VECs) in solid tumors and certain types of malignant tumor cells. Coagulation VII (FVII) can bind TF with high affinity, so the FVII-TF interaction provides an ideal target for therapy. Expression proteins skeletal muscles is a simple economical avenue continuous production therapeutic molecules. However, it difficult treat till now due limited number produced intramuscular gene expression system. Herein, we strived explore whether anti-tumor effects achieved via delivery plasmid encoding FVII-guided immunoconjugate (Icon) molecule previously established Pluronic L64/electropulse (L/E) technique. Our study exhibited several interesting outcomes. 1) The mouse light chain FVII (mLFVII) could guide red fluorescent protein (RFP) accumulate predominantly at sites TF-dependent manner. 2) Intramuscular mLFVII-hFc (human IgG1 Fc) Icon significantly inhibit growth both liver lung cancers nude mice, inhibition extent was proportional level tumor-expressed TF. 3) blood vessels amount flow were decreased Icon-treated mice. 4) This immunotherapy system did not display obvious side effects. provided efficient targeting It also open synergistic therapy conveniently integrating other anticancer regimens.