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Vaccination against cancer: COVID vaccines have opened the door

COVID vaccines advance cancer research

The mRNA vaccines were first used on a large scale in humans against the SARS-CoV-2 coronavirus. However, research on such vaccines was actually underway long before the corona pandemic. The global focus on this issue has given a huge boost to technology in this field. This could also lead to new vaccines against cancer in the foreseeable future. Expert Dr. Guido Wollmann explains the details.

Dr. Guido Wollmann is head of the Christian Doppler Laboratory for Viral Immunotherapy at the Medical University of Innsbruck. His area of expertise is so-called oncolytic viruses. This special type of viruses acts directly or indirectly against tumor cells. For more than a decade, researchers have been trying to use such viruses to treat or prevent cancer. The knowledge gained from the Corona vaccines could now bring a decisive breakthrough.

Expert interview with cancer researcher Guido Wollmann

Although the big breakthrough has so far eluded them, the results from decades of research into vaccines against cancer have been one of the reasons why the mRNA vaccines against SARS-CoV-2 have been able to get off the ground so quickly. Cancer researcher Wollmann explains why cancer research is now benefiting from the knowledge gained from the Corona mass vaccinations.

What stage are mRNA vaccines at against cancer?

“The three known mRNA vaccine manufacturers have a very strong background in cancer vaccination that has grown over the years,” Wollmann reports. One reason corona vaccine development has been so extremely rapid, he says, is in large part because these vaccine technologies are already well advanced in cancer therapy. According to Wollmann, these RNA platforms, which can then be individually equipped with RNA snippets of the corona virus or even of tumor mutations, had already been very well characterized in clinical studies involving thousands of cancer patients over many years.

How do the principles of action differ in cancer and corona?

“You put very short-lived genetic information into an mRNA vaccine, and your own body cell produces a protein with it,” the expert explains. This could be the information of a viral protein, for example, but also that of an altered component of an endogenous protein, namely that of a tumor mutation. So an mRNA vaccine could specifically encode the areas of a mutation against cancer. “These are tumor components that are only perceived by the immune system, but no longer have any function themselves,” the lab director emphasizes.

Injecting oncolytic viruses into the tumor

In addition to the mRNA vaccines, there are also so-called vector vaccines against SARS-CoV-2, whose mode of action differs. “For use in COVID vaccination, certain viruses are almost completely enucleated, filled with a small component of the genetic information of the COVID virus – in this case as a DNA piece instead of RNA – and used as a ferry,” Wollmann clarifies. The body still recognizes the unenucleated virus as a virus and generates an immune response.

“With oncolytic viruses, i.e. viruses that kill cancer, it’s different,” says the cancer researcher. They can’t be un-killed, he said, because they are designed to replicate exclusively in the tumor. In cancer research, therapies are currently being developed in which oncolytic viruses are injected directly into the tumor. There, they specifically attack the cancer cells and also trigger an inflammation that alerts the immune system to the tumor.

Are COVID vaccines advancing cancer research?

“Yes, very much so,” Wollmann emphasizes. According to the expert, all the very important, but also strict, regulatory processes represent a major burden for the large companies in the process of clinical testing phases and approval. That’s where it helps, he says, to be able to draw on the experience of millions of applications of these novel biological therapy platforms.

“Now you have additional arguments regarding the safety profiles,” Wollmann described. This mass vaccination takes away a lot of the concerns about these novel therapies. The Corona pandemic has also created a big lead in the upscaling process, that is, in upgrading operational facilities to produce large quantities of vaccine. That, he said, is an important future bonus for cancer vaccine development.

How does cancer research benefit on a technical level?

“Research on vector-based cancer therapies – that is, both cancer vaccines and oncolytic viruses – can learn in particular from the immunological interactions between the immune response against the target antigen, i.e., the corona or tumor protein, and the anti-vector immune response,” Wollmann said.

“A related and very topical further topic would also be the now intensively investigated application of COVID mixed vaccinations,” the expert further reports. This principle has been pursued in experimental cancer therapy for more than a decade, he said, and the ongoing studies worldwide on this approach would certainly promote the mixed use of cancer vaccines. You get clinical data on the body’s response to the vaccine combinations, he said, and you can draw parallels.

How does the immune system respond to adenoviruses?

COVID-19 vector vaccines use adenoviruses, which are likewise used for oncolytic viruses. “Everyone is exposed to adenoviruses all the time – these are the classic, mild cold viruses,” the scientist explains. The adenovirus generates very strong immunity, but not long-term immunity, he said. However, he said, there are very many adenovirus subspecies. The four adenovirus-based COVID vector vaccines currently approved in different parts of the world, are based in part on different adenovirus subtypes that tend to be very rare or not found at all in humans. In this way, he said, pre-existing immunity is circumvented.

“In tumor therapy, it has been shown that the intravenous administration of oncolytic adenoviruses very rarely leads to the desired reactions in tumor tissue, which is largely due to this certain pre-immunity against certain adenoviruses,” the expert explains. Because of the high probability of existing immunity, Wollmann says oncolytic adenoviruses as well as other oncolytic human viruses are injected directly into the tumor.

 

What are the side effects of cancer vaccines?

“Basically, compared to chemotherapy, the side effect profile of cancer vaccines or oncolytic viruses is much lower,” Wollmann emphasizes. You have treatment reactions that are part of the immune response that is triggered in the body, he says. These are predominantly flu-like symptoms, he says.

“The thing about RNA applications is that they are generally considered very safe,” Wollmann says. The extremely rare severe allergic reactions described, he said, are attributable to the nanoparticle shell, the protective bubble in which the RNA is located. After closer examination of these cases, he said, it became apparent that this particular allergic reaction only affected those people who had a history of allergic reactions to a component of these nanoparticles, namely the stabilizer polyethylene glycol (PEG). “Those affected already showed antibodies against this component,” Wollmann clarifies. If there is an injection of PEG with the vaccination, this could lead to an allergic reaction, he adds.

Are there approved viral tumor therapies?

“In 2015, a milestone was reached when the first oncolytic virus was approved for the treatment of black skin cancer in the United States and Europe,” Wollmann says. “T-Vec,” which is based on a modified herpes virus, is producing very good treatment success in a certain proportion of those affected, he says. The response rate, he says, is roughly in the range where so-called checkpoint inhibitors (immunotherapy form, note) have also revolutionized cancer therapy.

“In many cases, response means not only a prolongation of survival, but often also long-term control of the tumor to the point of cure,” the cancer researcher emphasizes. This is because, on the one hand, the viruses infect the cancer cells in the treated tumors in a highly specific manner and destroy them. For another, the viruses also trigger a very strong immune response against the tumor, preventing it from recurring elsewhere in the body, i.e., from metastasizing.

“That is the great promise of these oncolytic viruses,” sums up the head of the Christian Doppler Laboratory for Viral Immunotherapy. In the meantime, he says, almost all clinical studies on oncolytic viruses are combined with immunotherapy.

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