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Several cancer researchers have already created “smart bombs” that allow for the orderly release of two different anti-cancer drugs.
But scientists say the missing person is the “stealth bomber” – a delivery system that can sneak through the body’s radar defenses. And now they believe that the newly modified virus could eliminate tumor growth in patients with metastatic cancer.
“This is a new way of treating metastatic tumors. It can be armed with genes and proteins that stimulate cancer immunity, and the virus coat can be assembled, as if you were putting lego cubes,” he said. said lead author Professor Dmitry Shaykhmetov of the Emory University School of Medicine in the United States.
The importance of cancer-killing viruses, known as cancer-causing viruses, has been debated and tested for decades.
One of these viruses was approved by the Food and Drug Administration (FDA) in 2015 against skin cancer.
The body’s defense system quickly picks up viruses injected into the bloodstream and sends them to the liver, which is the body’s waste disposal system.
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Now, researchers have found a way to redesign the virus delivery system so that the virus is not easily captured by parts of the immune system. This allows the virus to be injected into the blood without causing a severe inflammatory reaction.
Professor Shaykhmetov said: ‘The innate immune system is very effective at sending viruses to the liver when they are administered intravenously. For this reason, most cancer viruses are transferred directly to the tumor, without affecting metastasis. A in turn, we believe it will be possible to systematically deliver our modified virus. In doses high enough to suppress tumor growth, without causing life-threatening systemic toxicity. “
The study includes a structure for the redesigned conduction system and the ability of the virus to eliminate tumors spread to mice.
Scientists focused on redesigning adenovirus, a delivery system used in dozens of cancer clinical trials, to stimulate the host’s antitumor response.
Adenoviruses have also been central in gene therapy studies.
Shaikhmetov recalls the death of Jesse Gelsinger during a 1999 clinical trial of gene therapy.
The volunteer died from a cytokine storm and multi-organ failure associated with high doses of an adenovirus vector released into the bloodstream.
“This event inspired me to retool the adenovirus so that it doesn’t cause a strong inflammatory reaction,” said Shaikhmetov. It sees the redesigned adenovirus as a technology platform, which can be adapted and customized for many types of cancer and also for individual cancer patients as a form of cancer treatment.
Shaikhmetov began working on modified virus technology while at the University of Washington and founded a company, AdCure Bio, to provide a potentially life-saving treatment for patients suffering from common diseases.
And in 2012, he published research on how adenovirus interacts with a single host factor in the blood, coagulation factor X, in Science.
Professor Phoebe Stewart, co-author of the study, of Case Western Reserve University in Cleveland, Ohio, said, “Sometimes, even small changes in structural proteins can be catastrophic and prevent the infectious virus from clustering. In this case, we have modified adenoviruses in three places.To reduce the virus’s interactions with specific blood factors, we found that the virus is still aggregating and remains effective at infecting and killing cancer cells.
A slower adaptive immune response to the modified virus is still possible, similar to what is observed in the vaccine.
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Researchers say a combination of viruses could be used among cancer patients to extend therapeutic benefits.
“Our study is the first to show that we can modify the natural association of IgM with adenovirus. We have introduced mutations that prevent the inactivation of the virus in the bloodstream and trap it in liver macrophages, which is the largest concentration of immune cells in our body that besiege and destroy pathogens, ”said Shaikhmetov. It is that any regular repetitive structure, such as the envelope of the virus, would attract a low bond with natural IgM antibodies, leading to their immediate inactivation and removal from the blood. “
The researchers also replaced a portion of the adenovirus that interacts with human cell integrins (membrane proteins embedded in the plasma membrane of living cells) and replaced a sequence of another human protein that targets cancer cells with the virus.
When injected into mice, the high doses of standard adenovirus caused liver damage and death within days, but the modified virus did not.
The modified virus can eliminate tumors spread by some but not all mice implanted with human lung cancer cells.
A complete response was seen in approximately thirty-five percent of the animals. The scientists found that the tumor sites in the lung turned into scar tissue.
Now, Professor Shaikhmetov’s lab is exploring ways to increase the overall response rate.
The findings are published in the journal Science Translational Medicine.
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