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Genetically engineered herpes virus may be used in cancer fight

Viruses can make animals and humans sick – or healthy: Researchers at the Fraunhofer Institute for Interfacial Engineering and Biotechnology (IGB) have succeeded in genetically modifying the herpes simplex virus type 1, which triggers painful cold sores, so it can be used in the future in the fight against cancer.

Viruses have a simple structure: They consist of a small amount of genetic material wrapped in proteins and lipids. Measuring just 20 to 200 nanometers, they can only be detected using an electron microscope. Yet their ability to take over living cells and exploit them to multiply is what makes viruses unique. They often destroy their host cells in the process, and that’s when animals and humans get sick – or now, healthy: Professor Susanne Bailer and her team at the Fraunhofer IGB in Stuttgart have succeeded in genetically modifying the virus of herpes simplex type 1 so that it can be used as an effective weapon against tumor cells.

Stopping pathogenic genes in their tracks

The herpes virus is known for the painful and unsightly blisters it causes on the lips. However, herpes viruses can also cause encephalitis, especially in people with weakened immune systems. Professor Bailer, who leads the Virus-based Technologies innovation unit at the Fraunhofer IGB, has achieved a real feat: She managed to deactivate the genes of the virus that caused the disease, thus making it treatable. The genetic material of the herpes virus is made up of DNA, not RNA as in the case of the SARS-CoV-2 coronavirus, for example.

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“The DNA genome is much larger than the RNA genome, which means that many additional genes can be accommodated there. So when we seek to reprogram the virus, we have a lot of genes at our disposal,” says Professor Bailer, who has been researching herpesviruses for 20 years.

Another advantage is that the basic technologies that can be used to genetically modify herpes viruses already exist. Supported by the development of the COVID-19 vaccine, significant progress has been made in this area of ​​research in recent years. AstraZeneca’s vaccine is based on adenoviruses, which cause colds in chimpanzees but are harmless to humans. The modified viruses transmit to human cells the information necessary for the development of vaccine antigens, which makes it possible to form antibodies specific for SARS-CoV-2. Overall, Professor Bailer believes AstraZeneca’s success has spurred research into genetically modified viruses and largely dispelled earlier fears.

Oncolytic virotherapy to stimulate the body’s immune defenses

Professor Bailer and his team have succeeded in improving the genetic engineering methods used to manipulate herpes viruses, allowing them to incorporate target control.

So when we inject our viruses directly into the tumour, they enter the cancerous cells and not the healthy cells. They then multiply and cause the cells to burst. »

Prof. Susanne Bailer, Fraunhofer IGB

This process releases tumor markers that allow the body’s immune system to fight cancer. “In addition, we activate the immune response with specific proteins that our viruses release when they reproduce. The immune system then recognizes the tumor cells and eliminates them. Prof. Bailer also hopes to use this process to combat undetected metastases outside the tumor site. “The immune system is the most powerful weapon we have to fight cancer. Using our virus and released tumor markers, we seek to stimulate the immune system in a targeted manner so that the body can essentially treat itself. »

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First successes in the fight against lung cancer

The first preclinical tests using the so-called oncolytic virus were carried out by the Fraunhofer IGB team as part of the TheraVision project, in cooperation with the Fraunhofer Institutes for Cell Therapy and Immunology IZI, Toxicology and experimental medicine ITEM, and silicate research ISC. The researchers designed the virus specifically for use in the treatment of non-small cell lung cancer. The mortality rate for this type of cancer is high. Only 22% of female patients and 17% of male patients survive the first five years after lung cancer diagnosis, and the prognosis is even worse for non-small cell carcinoma due to early metastasis .

Viral immunotherapy may also prove effective against metastases

The results of the studies are promising. Tumor cells were successfully eliminated, and viral immunotherapy might also be effective against metastases. “We need to investigate this further,” says Professor Bailer. It is still too early to proceed with clinical trials. However, the outlook for this is good, because the herpes simplex virus has another decisive advantage over other viruses: we can press an “emergency stop button”. If unexpected side effects occur while treating debilitated cancer patients, there is a reliable way to stop the process of viral multiplication using a highly effective antiviral drug that has been proven for almost 50 years. However, further studies will need to be conducted before it can be used in a clinical setting: “We need to better understand the mechanisms of action to unlock the full potential of viral immunotherapy. Anyway, we have now developed a viral technology platform that can be used for other types of tumors in the future. »

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