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STUTTGART – 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 causes painful cold sores, so that 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 surrounded by proteins and lipids. A mere 20 to 200 nanometers in size, they can only be seen with an electron microscope. But what makes viruses unique is their ability to board living cells and use them to reproduce. They often destroy their host cells in the process. Then animals and people get sick – or get well: Prof. Susanne Bailer and her team at the Fraunhofer IGB in Stuttgart have succeeded in genetically modifying the herpes simplex virus type 1 in such a way that it can be used as an effective weapon against tumor cells.
Turn off disease-causing genes
The herpes virus is known for the painful, unsightly blisters it causes on the lips. Especially in people with a weakened immune system, herpes viruses can also trigger encephalitis. Bailer, who heads the “Virus-based Technologies” innovation field at the Fraunhofer IGB, has achieved a feat: she switched off the genes of the virus that cause disease – and thus made them usable for therapy.
The genetic material of the herpes virus consists of DNA, not RNA like the SARS-CoV-2 coronavirus, for example. “The DNA genome is much larger than the RNA genome, which means numerous additional genes can be accommodated there. So if we want to reprogram the virus, we have a large memory available," explains Bailer, who has been researching herpes viruses for 20 years. Another advantage: The basic technologies with which herpes viruses can be genetically modified already exist. Promoted by the development of the corona vaccine, research has made great progress here in recent years. The AstraZeneca vaccine is based on adenoviruses, which cause colds in chimpanzees but are harmless to humans. The modified viruses smuggle the necessary information for the construction of vaccine antigens into human cells, whereupon SARS-CoV-2-specific antibodies are formed. In general, Bailer believes, the success of AstraZeneca has encouraged research into genetically modified viruses and largely dispelled previous reservations.
Tumor markers and proteins stimulate the body's own immune system
Bailer and her team succeeded in improving the genetic engineering methods for manipulating the herpes virus. So they could program a target control. “This ensures that our viruses, which we inject directly into the tumor, penetrate cancer cells and not healthy ones. There they multiply and cause the cells to burst.« This releases tumor markers that position the body's own immune system in the fight against cancer. “We also activate the immune system with specific proteins that our viruses release during reproduction. The immune system then recognizes the tumor cells and eliminates them.” »The immune system is our strongest weapon against cancer.
First successes against lung cancer
The Fraunhofer IGB team carried out the first preclinical tests with the so-called oncolytic virus in the TheraVision project, in cooperation with the Fraunhofer Institutes for Cell Therapy and Immunology IZI, for Toxicology and Experimental Medicine ITEM and for Silicate Research ISC. The researchers specified the virus for the treatment of non-small cell lung cancer. Mortality from this type of cancer is high: only 22 percent of all patients and 17 percent of all patients survive the first five years after the diagnosis of lung cancer. The prognosis for non-small cell carcinoma is even worse because of its early metastasis formation.
Viral immunotherapy could also work on metastases
The results of the studies are promising. The tumor cells were reliably destroyed, and virus immunotherapy seems to be effective even in the case of metastases. "We still have to investigate this further," Bailer admits. It is still too early for clinical testing. However, the prerequisites for this are good, because the herpes simplex virus offers another decisive advantage over other viruses: there is a kind of “emergency brake”. If unforeseen side effects should occur during the therapy of weakened cancer patients, the multiplication of the virus can be reliably stopped with an extremely effective antiviral drug that has been tried and tested for almost 50 years.
However, further studies are necessary before it can be used in the clinic: “We need to better understand the mechanisms of action in order to leverage the full potential of virus immunotherapy. In any case, we have now developed a virus platform technology that can also be used for other types of tumors in the future.