Beata Halassy: virologist who cured her cancer with experimental therapy: promises and limitations of the study

• What happened: virologist Beata Halassy from Zagreb tested experimental virus therapy against cancer (oncolytic virotherapy) on herself, because it was determined that her breast cancer had returned
• Why this is important: She has been healthy for four years after the therapy, which would mean that the therapy was successful.
• What is the problem: one problem is the bioethicality of experimenting on oneself, and the other problem is that the case study work is on only one person and it is necessary to conduct wider clinical studies to really determine the effectiveness and safety of the therapy.

 

Beata Halassy, ​​a virologist from the University of Zagreb, faced another merciless battle – this time, perhaps the most difficult in her life. Her story is not only a case study of courage and innovation, but also a powerful testimony of a woman who decided to confront a deadly disease in her own way, using the tools of her life's calling.

It all started in 2020, when Beata, after several years spent fighting breast cancer, again felt discomfort in the place where she had previously been operated on. She already had a mastectomy on that part of her body and went through a long and exhausting recovery process. When she felt the pain and the lump, her heart sank. She went in for a check-up, hoping for the best but fearing the worst. The diagnosis was merciless: the cancer had returned.

This time, it was in the third stage, more serious and dangerous than before. Beata was faced with a difficult decision – the doctors recommended a new operation, which would be followed by even more aggressive chemotherapy. Even though she knew it was standard therapy, the idea of ​​going through arduous cycles of chemotherapy and grueling side effects again threw her into despair. She felt that she had less and less strength for a new round of the same painful struggle.

Beata was trying to find an alternative. She thought about how she might be able to use her own expertise and years of experience in virology. As a virologist, she has spent years studying how viruses affect cells and how they can be modified in the laboratory. She couldn't ignore the question in her mind: what if the virus could help fight her cancer?

What is onlolytic virotherapy (OVT)?

The idea of ​​oncolytic virotherapy (OVT), an experimental therapy that uses viruses to attack tumor cells, is attracting increasing interest from scientists around the world. In the US, the Federal Food and Drug Administration (FDA) has already approved one virus-based cancer therapy against melanoma. It is T-VEC (also called Imlygic and Talimogene laherparepvec), which is based on an oncolytic herpes virus that has been genetically modified.

The idea of ​​oncolytic virotherapy is therefore not new, but there are still not many clinically proven cancer therapies based on viruses. A lot of controversy was associated with Rigvir, a therapy from Latvia, and it did not become commercially available, it even caused an affair, and many oncologists expressed concern about the effectiveness and safety of the therapy.

The term oncolytic therapy would literally mean “ cancer therapy with cancer-destroying viruses”. This is a newer approach in cancer therapy and is still developing. The thing with these therapies is that they can act on the microenvironment of the tumor in several ways – from the fact that the genetically modified virus itself acts on the cancer cells, to the fact that the action of the virus stimulates the immune system, raises it to a higher level of alertness, and then the cells of the immune system destroy the cells cancer.

However, the problem is that the development of such therapies is still in its infancy.

Measles virus and vesicular stomatitis virus in the cocktail of breast cancer therapy

Beata knew that research on this type of treatment was increasing, but most clinical trials were focused on the late stages of metastatic cancer. However, this therapy has not yet become widely applicable, and was certainly not an option for self-treatment. Nevertheless, Beata was determined to find a way out. The decision to try something different became her path.

With the help of colleagues from the laboratory, Beata started working on her own virus “cure”. They devised a way to combine the measles virus (measles, MeV), which is known for its oncolytic effects, with the vesicular stomatitis virus (VSV), which is a pathogen similar to the flu. Together, these viruses were known for their ability to infect and destroy cancer cells. In addition to all that, she also had a clear picture of how viruses could stimulate the body's immune response to attack a tumor. The combination of these viruses could attack cancer cells from two sides: directly destroying the tumor and stimulating its immune system to react.

Some neurotoxicity has been recorded with VSV in primates, but only when directly applied to the nervous system. Neurotoxicity was not observed when administered by injection into the tumor. The Edmonston-Zagreb strain was used as the measles virus, which was once used for the production of measles vaccines, when they were produced at the institute in Zagreb.

The story of Beate Halassy, ​​who bravely took the risk of self-treatment using her own experimental therapy, was published as a case study in the journal Vaccines under the title “An Unconventional Case Study of Neoadjuvant Oncolytic Virotherapy for Recurrent Breast Cancer“. By the way, the work was initially rejected by several journals due to bioethical dilemmas.

“The Edmonston-Zagreb measles virus vaccine strain is known for its safety in pediatric vaccines that have been used for more than 40 years. Breast carcinomas abundantly express the surface receptors CD46 and nectin-4, which the measles vaccine strain in particular, especially viruses from the Edmonston line, use to enter cells. Therefore, the use of the Edmonston-Zagreb strain was considered appropriate. In addition, measles virus oncolytic virotherapy (OVT) has been clinically tested in patients with advanced stages of various types of breast cancer. VSV is a pathogen of animals, but is almost non-pathogenic to humans and at worst causes flu-like symptoms. It was shown to provide protection against reinfection in a mouse model of breast cancer ,” the authors state in the paper.

So, let's be clear – what Halassy and her colleagues did is not exactly the domain of so-called “ garage or Do-it-yourself” biology. They all had very deep knowledge of the area and knew what they were doing. This case should by no means be an incentive for someone to make their own virus-based therapy, because they probably just don't have that good knowledge and technology. The viruses used in the therapy were not genetically modified, which is a different approach than T-VEC, where the herpes virus is genetically modified to improve its oncolytic properties.

In the laboratory, her colleagues carefully cultivated the viruses and prepared them for injection. So Halassy didn't do it all by herself.

Months passed, and Beata noticed changes. The pain subsided, and the tumor began to shrink. Examinations were carried out, and the results showed positive signs. Finally, after four years, her status became stable – the cancer was no longer present. Today, she is still cancer-free.

What should be paid attention to in this work?

It should be noted that in the paper it is nicely written that Halassy also received conventional therapy with the drug trastuzumab during oncolytic therapy:

“Due to the HER2 3+ phenotype of the excised tumor, the patient additionally completed a one-year adjuvant therapy with trastuzumab, in accordance with the recommendations for the treatment of HER2 3+ breast cancer ,” the paper states.

This means that the cure cannot be fully attributed to oncolytic therapy, nor can this treatment be interpreted as an alternative, but rather the development of an additional therapy.

And not only that: there are a number of other things to pay attention to in order to better understand this work and the scope of the therapy.

“It is important to know that this is only one experiment, that it is primarily interesting to researchers who are involved in the development of this type of cancer therapy, and that I hope that the published results could speed up the development of this type of treatment ,” said Dr. Beata Halassy in a short email that was the answer to my inquiry. What does this mean?

Well, evidence in medicine has its own weight and varies. Some holy grails of evidence are randomized double-blind clinical trials. That and of course metastudies, which combine the evidence of several randomized studies, are a very high level of evidence. However, case studies, such as this one and as emphasized in the title of the paper, on one patient, are actually a low level of evidence. And dr. Halassy knows this and emphasizes it. In order to know how effective these therapies are, we need a slightly larger sample of patients, not just one. The next step would be research on a group of patients. That is, one swallow does not make a spring in science and medicine. The results must have a better statistical basis, be repeatable, with a similar result, and not just a coincidence.

Experimentation on oneself carries with it bioethical doubts. This procedure is a bit like science fiction movies when some doctor injects himself with something and gets some superpower or turns into something. But in reality, there are cases of doing experiments on oneself. Jesse Lazear proved that mosquitoes transmit yellow fever by deliberately exposing himself to mosquitoes – he died 17 days later of yellow fever. Max Pettenkofer drank broth with the causative agent of cholera because he was in a discussion with Robert Koch about the cause of the disease. While Koch argued that cholera was caused by bacteria, Pettenkofer sided with the theory that the cause was environmental. He contracted a mild form of cholera and fortunately survived. He claimed it wasn't even cholera, but modern interpretations still say it was cholera, and he was lucky to get a mild form.

This pioneering attempt at therapy opened up a debate in the medical community. While some experts are fascinated by its success, others express concern about the risks that come with self-medicating with unsupervised oncolytic virotherapy. The authors of the study emphasized that such an approach carries significant risks and is not recommended without medical guidance.

What do bioethicists say?

For Science Speaks, I reached out for an answer from one of today's leading bioethicists, Professor Arthur Caplan from the NYU Grossman School of Medicine – Langone Medical Center, who of course followed the case, which Nature also wrote about . Nature, however, incorrectly wrote that Halassy herself grew the viruses, while in reality her colleagues did it.

“There are two problems with auto-experimentation. The first is that any individual scientist or doctor is often not in a position to know what might be safe and effective. In this case she was, but often the risks are much higher and the unknowns are huge. Second, an experiment on one provides little information about generalizing to others. If you test positive on yourself, the next step is not to immediately try it on others, but to put the drug into a clinical trial to see if other people will; sicker, older, heavier, dying; to answer or not and which dose is optimal. It's brave to self-experiment, but it should be seen as a step toward testing in a systematic way if it seems to work ,” Dr. Caplan replied in an email.

Despite the divided opinions, Beata's story has inspired many battling cancer, as well as scientists researching alternative therapies. Her path was full of uncertainty, but through her courage and persistence, Beata Halassy became a symbol of hope and the spirit of exploration. Although she did not expect that one day she would apply her knowledge to her own life, Beata proved that science and passion can open doors to new possibilities, even in the darkest moments.