March 02, 2013
Newcastle Virus Modified To Kill Only Prostate Cancer Cells

An ideal cure for cancer will only kill cancer cells while leaving all other cell types alone. It is quite difficult to develop such a narrowly targeted anti-cancer agent. However, some VPI researchers have genetically modified a virus so that it selectively targets and kills only prostate cancer cells.

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.

Viruses have surface fusion proteins which enable viruses to enter cells. The researchers modified the Newcastle virus' fusion protein so it would become activated by the prostate specific antigen found only on prostate cells. So the virus only enters prostate cells.

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.

Proteases slice into a protein and can activate or deactivate the protein by doing this depending on where they slice and how the protein is structured. Not all types of cancers are necessarily going to have a cell surface protease that can be harnessed to target just one cell type.

Share |      Randall Parker, 2013 March 02 09:58 PM 


Comments
Phillep Harding said at March 3, 2013 5:48 PM:

Well, now. This looks promising. Now if I can just hang on until it's ready for release...

destructure said at March 4, 2013 8:49 AM:

Prostate cancer is the most common non-skin cancer in America, affecting 1 in 6 men. The obvious question is whether researchers can engineer virus to attack other kinds of cancers. So this is huge.

Mthson said at March 5, 2013 5:56 AM:

Best of luck, Phillep Harding. I've enjoyed your comments over the years!

Phillep Harding said at March 5, 2013 11:14 AM:

Thnx. The circle closes, but it's still scary sht.

Brett Bellmore said at March 5, 2013 4:46 PM:

If I'd only known, I wouldn't have hurried my prostate surgery. Of course, my lymphoma was only discovered because of the pre-operative physical for that surgery, so if I'd known I might now be dead...

Randall Parker said at March 8, 2013 8:30 PM:

Phillep,

It is worth looking at web sites where clinical trials get announced. You can get years ahead of the pack by doing a clinical trial.

Brett,

I'll keep an eye out for promising new lymphoma treatments too. Here's one. Here's another at an earlier stage of development that uses nanoparticles to trick lymphoma cells into thinking the anti-cancer drug is really HDL cholesterol.

Phillep Harding said at March 9, 2013 12:13 PM:

My medical oncologist is inclined to use them when possible. He suggested one once and I reacted before thinking, remembering some of the horror stories from the 50's and 60's (some of those trials should have brought murder charges).

I plan to speak with him about what's available, the latest experimental drugs just lost effect and he wants me to come in. I may be off the net for a while, depending on what happens next.

Phillep Harding said at March 21, 2013 5:32 PM:

Well, the oncologist never heard of the Newcastle trials, but thinks it's an excellent approach. I've heard elsewhere of medical trials involving injecting salmonella in melanomas, it's supposed to kill all melanomas in the body. Sort of questionable in my mind; cancers mutate constantly, so what hits one might not effect another.

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