Scientists Solve Structure of Oncolytic Lung Virus; Plan Viral Attack on Lung Cancer

Here’s an interesting, and promising, new way to tackle lung cancer. At Argonne National Laboratory scientists have deciphered the structure of a virus that seems to selectively infect small-cell lung cancer cells. The virus, known as Seneca Valley Virus-001 (or NTX-010) was originally identified by a company called Neotropix out of Malvern, Pennsylvania. According to Neotropix, who is the owner of NTX-010, this unique pathogen…

“…is the only oncolytic virus that is not inhibited by any component of human blood that would prevent the virus from circulating, reaching tumor masses, and infecting them at reasonable doses. Systemic delivery is the only route of administration to reach all metastases in the body. NTX-010 can be delivered systemically and does not require intratumoral delivery like most other oncolytic viruses in development. NTX-010 is also unique in that it can be produced to an extremely high level in cell lines that have already been approved by the FDA as suitable cell lines for manufacturing. Since it is a native, unaltered virus, there is no chance to generate recombinants as observed for other viruses. Finally, NTX-010 targets cells having altered pathways known to be critically involved in metastases and invasion. “

More from Argonne NL about the effort to identify the structure of the virus:

The 3-D structure of the virus, known as Seneca Valley Virus-001, reveals that it is unlike any other known member of the Picornaviridae viral family and confirms its recent designation as a separate genus "Senecavirus." The new study reveals that the virus’s outer protein shell looks like a craggy golf ball­—one with uneven divets and raised spikes—and the RNA strand beneath it is arranged in a round mesh rather like a whiffleball.
"It is not at all like other known picornaviruses that we are familiar with, including poliovirus and rhinoviruses, which cause the common cold," says the study’s senior author, Associate Professor Vijay S. Reddy, Ph.D., of The Scripps Research Institute. "This crystal structure will now help us understand how Senecavirus works and how we can take advantage of it."
The Senecavirus is a "new" virus, discovered several years ago by Neotropix Inc., a biotech company in Malvern , Pa. It was first thought to be a laboratory contaminant, but researchers found it was a pathogen, now believed to originate from cows or pigs. Further investigation found the virus was harmless to normal human cells, but could infect certain solid tumors, such as small-cell lung cancer, the most common form of lung cancer.

Scientists at Neotrophix say that, in laboratory and animal studies, the virus demonstrates cancer-killing specificity 10,000 times higher than seen in traditional chemotherapeutics, with no overt toxicity. The company has developed the "oncolytic" virus as an anti-cancer agent and is already conducting early phase clinical trials in patients with lung cancer.
But the researchers still did not know how the virus worked, so they turned to Reddy. He and his Scripps Research team, especially Sangita Venkataraman, Ph.D., a postdoctoral researcher, determined the Senecavirus crystal structure.
Reddy describes the differences they found between other picornaviruses and the Senecavirus as like variations among car models of the same manufacturer. "The chassis is the same, but the body style is different," he says. "How the body of a virus is shaped determines how it infects cells."
The structure of the Senecavirus is also depicted at http://viperdb.scripps.edu/ , the "Virus Particle Explorer" developed at Scripps Research by Reddy and his colleagues. The online database is a worldwide resource for information on the structure of viral particles; it contains details of 253 viruses to date.

Argonne press release: Researchers seek to understand and improve virus that infects lung cancer cells …
Neotropix Technology Platform …
Structure of Seneca Valley Virus-001 @ VIPERdb…