Stealth virus for cancer therapy

January 31, 2018

Viruses have their own genetic material and can infect human cells in a very specific manner. They will then reproduce as directed by their own genes but using the resources of the host cell. These properties make them interesting "gene shuttles" to fight hereditary diseases or cancer. There are innumerable different viruses, but the human adenovirus 5, which normally causes the symptoms of a typical cold, has substantial advantages: Its genome can be replaced completely by an artificial one which contains only "useful" genes. Without any of the viral genes left, the virus can no longer replicate and trigger diseases. In addition, the genome of the adenovirus is very large and does not integrate into human chromosomes.

Adapter molecules dock the virus to the tumor

Until now the use of adenoviruses in tumor therapy has been very limited. They lack the ability to infect cancer cells and therefore cannot inject the genetic blueprints for the therapeutic molecules to fight the disease. Moreover, adenoviruses are efficiently neutralized by the immune system and very rapidly eliminated by the liver. Researchers led by Andreas Plueckthun, professor at the Department of Biochemistry at the University of Zurich, have now succeeded in rebuilding the viruses so that they effectively recognize and infect tumor cells. "For this purpose we have created molecules which act as an adapter between the virus and the tumor cell," explains Markus Schmid, first author of the study.

The adapters, which cling very tightly to the coat of the virus, can - depending on their version - bind to different surface molecules on the tumor cell. The scientists tested adapters for several receptors such as HER2 and EGFR, which are present on various types of cancer cells. Only viruses which were equipped with these adapters were able to infect the tumor cells.

New protein shield masks and protects against the immune system

In a next step the researchers hid the virus under a novel protein coat, which serves as camouflage for the virus and which protects it from the immune system. As a basis for this shield the researchers used an existing antibody that they redesigned. In an interdisciplinary collaboration between the different research teams, the exact architecture of the complete protective coat was described almost down to the level of atoms.

The shield does not only protect the redesigned virus from the immune cells but also prevents the virus from being eliminated by the liver, which normally quickly removes unmodified adenoviruses from the bloodstream, often making therapeutic applications impossible. The virus, redesigned using sophisticated protein engineering techniques, works: With its shield and its adapter, these viral gene shuttles efficiently infected tumor cells in laboratory animals.

Valuable tool for gene therapy of aggressive tumors

Using these stealth gene shuttles, the UZH scientists want to develop novel therapies for different types of cancer. The numerous advantages of adenoviruses will likely help to tackle one of the greatest problems of cancer medicine: The development of resistances against drugs. Biochemist Andreas Plueckthun is optimistic: "With this gene shuttle, we have opened up many avenues to treat aggressive cancers in the future, since we can make the body itself produce a whole cocktail of therapeutics directly in the tumor."
-end-


University of Zurich

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.