University of Pittsburgh researchers have discovered that Vesicular Stomatitis Virus G glycoprotein (VSV G) can be modified to specifically target cancer cells expressing the transmembrane glycosylated tyrosine kinase, HER2/neu.
Description
It has been discovered that the LDL receptor (LDL-R) is a major binding site for the Vesicular Stomatitis Virus (VSV). By removing the LDL-R binding site in VSV G glycoprotein and adding a sequence coding for a specific single chain antibody (SCA), a replicating recombinant VSV, rrVSV G, specifically targeting cancer cells can be developed leading to more targeted treatment approaches.
Applications
1. Personalized cancer therapy
2. Immunotherapy
Advantages
Viral oncolytic immunotherapy, the use of viruses to specifically target and kill cancer cells, is a growing area of pre-clinical and clinical research. However, safety remains a key concern given many cancer patients will be immunocompromised. To overcome this, using viruses that can specifically target cancer cells over healthy cells are the best approach. Additionally, using viral vectors that do not produce serious human disease is key.
This approach uses VSV, an efficient cell killer which does not produce a serious human disease and has no risk of host cell transformation. VSV can be successfully modified to target specific cancer cells through targeting of unique proteins expressed in those cells. This approach will lead to selective targeting of diseased cells over healthy cells.
Invention Readiness
In vivo experiments have shown therapeutic benefit in preclinical mice studies. Human studies are required. Previous research has shown that wild type VSV has the potential for neurotoxicity. The subsequent development of recombinant attenuated VSV has been shown to cure implanted peritoneal tumors in mice and could potentially reduce neurotoxic risk.
Further modifications involving elimination of genes that mediate LDL-R binding and addition of genes coding for an SCA produced a new immune-stimulating oncolytic virus specifically targeting Her2/neu expressing cancer cells and tumors. Animal studies showed this rrVSV-G was able to cure very large, implanted multinodular tumors and provided permanent anti-tumor immunity.
IP Status
Patent Pending
