Peregrine Pharmaceuticals, Inc said the publication of a report in a recent issue of "Cancer Research" showing that different antibody-based targeting agents can be used to effectively deliver the coagulation protein truncated tissue factor (tTF) to tumours for the treatment of cancer.
The study also highlights the effectiveness of delivering agents to tumours that block blood flow to the tumour resulting in therapeutic effects, which is the concept behind Peregrine's Vascular Targeting Agent (VTA) technology. Peregrine has been researching the use of truncated tissue factor as an anti-cancer compound that selectively causes blood clots to form within tumour blood vessels, thus cutting off oxygen and nutrients to tumor cells and causing tumour cell death.
In the report, truncated tissue factor was linked to several antibodies that target tumors or tumor vasculature. The targets studied included markers of tumor blood vessels and structures found in the necrotic core of solid tumours. Tumour blood vessels were selectively blocked by the antibody targeted tissue factor while vessels in normal tissues remained open. In the study the tumours turned black within hours and regressed in size rapidly which has been observed in other tTF treatments. The results of the study demonstrated a significant therapeutic effect in lung and colon carcinoma tumor models. Pre- clinical data on Peregrine's VTA technology previously published in "Science" showed that antibodies attached to tTF also had significant anti-tumour effects. In the "Science" study, 38% of treated mice had complete tumour regressions. An additional 24% of the mice treated had at least a 50% reduction in tumor mass.
Alan Epstein, MD., PhD., professor of pathology at the Keck School of Medicine of the University of Southern California (USC), the inventor of Peregrine's Tumour Necrosis Therapy (TNT) targeting platform and a co-author on the new published report, said, "This work further indicates the potential of truncated tissue factor as a therapeutic agent for tumor therapy and a potential new use of the TNT targeting platform. The new article and our prior research experience demonstrates that multiple targets exist which can be used to localize tTF to occlude tumour blood vessels."
The blood coagulation cascade (blood clotting) is a normal process that the body uses to stop the flow of blood from damaged tissue. When blood vessels are damaged during injury, factors in the blood come into contact with Tissue Factor (TF) found on cells normally found outside the blood vessels. TF is a receptor protein that is the initiator of the extrinsic pathway of the blood clotting. A truncated derivative of Tissue Factor (tTF) has been developed by Peregrine in which the portion of the TF molecule that tethers it to the surface of cells has been removed. Since tTF is soluble (not associated with a cell membrane that is necessary for induction of clotting), the tTF is usually inactive when injected into the blood stream. Using Peregrine's VTAs, a targeting antibody is substituted for the membrane attachment region of the TF molecule allowing it to be selectively delivered to tumour blood vessel cell surfaces where it can initiate clotting that results in an avalanche of tumor cell death.