A recombinant Newcastle disease virus kills all kinds of prostate cancer cells, including hormone resistant cells, but leaves normal cells unscathed, according to a paper published online ahead of print in the Journal of Virology. A treatment for prostate cancer based on this virus would avoid the adverse side effects typically associated with hormonal treatment for prostate cancer, as well as those associated with cancer chemotherapies generally, says corresponding author Subbiah Elankumaran of Virginia Polytechnic Institute, Blacksburg. The modified virus is now ready to be tested in preclinical animal models, and possibly in phase I human clinical trials.
Newcastle disease virus kills chickens, but does not harm humans. It is an oncolytic virus that hones in on tumors, and has shown promising results in a number of human clinical trials for various forms of cancer. However, successful treatments have required multiple injections of large quantities of virus, because in such trials the virus probably failed to reach solid tumors in sufficient quantities, and spread poorly within the tumors.
The researchers addressed this problem by modifying the virus's fusion protein. Fusion protein fuses the virus envelope to the cell membrane, enabling the virus to enter the host cell. These proteins are activated by being cleaved by any of a number of different cellular proteases. They modified the fusion protein in their construct such that it can be cleaved only by prostate specific antigen (which is a protease). That minimizes off-target losses, because these "retargeted" viruses interact only with prostate cancer cells, thus reducing the amount of virus needed for treatment.