From Laboratory to Market: The Journey of Antibodies Developed by VU Scientists

Prof. Aurelija Žvirblienė with her team

Prof. Aurelija Žvirblienė, head of the Department of Immunology at the Life Sciences Center of Vilnius University (VU), and her team have developed hundreds of unique antibodies targeting viral and bacterial proteins, recombinant cytokines, cell receptors, and allergens.

‘Over more than two decades, we have created a wide range of antibodies, some of which have been successfully commercialised for companies. These antibodies can be used in diagnostics and further scientific research,’ said Prof. Žvirblienė, noting that the development, engineering, and application of antibodies is one of the main research directions in her department.

Antibodies and macrophages are the key players in our immune system

We all have a vast array of different antibodies – these are proteins produced by B lymphocytes in our bodies. B lymphocytes are the only cells capable of secreting antibodies; this process continuously occurs in our bodies.

‘When B lymphocytes are activated, they begin secreting antibodies that perform various functions. Perhaps the best-known function is the neutralisation of bacterial toxins or the ability of antibodies to bind to viruses and prevent them from infecting our cells. Antibodies are constantly produced in our bodies and are a vital component of our immune system,’ noted the Professor.

It is essential to understand that antibodies bind specifically to the antigen that triggered their production.

‘If we have recovered from COVID-19, our bodies have produced antibodies that recognise the virus that caused it. However, these antibodies will not protect us from flu or a staphylococcal infection,’ emphasised the researcher.
Antibodies are specific molecules that bind only to their target, and it is this property that allows scientists to use antibodies to detect particular substances.

‘In our lab research, we develop antibodies that are directed against specific antigens. This enables us to apply these antibodies to identify those antigens,’ explained the Professor.

The department headed by Prof. Žvirblienė also conducts fundamental research to understand how our immune system functions, how its components respond to viral antigens, and what molecular mechanisms are activated.

‘We focus primarily on the part of the immune system that responds very quickly to infections –innate immunity. One of the key components of the innate immune system is macrophages, which are capable of rapidly detecting foreign pathogens and reacting accordingly. During infections, symptoms such as fever are often the result of macrophage activation. Therefore, together with colleagues, we use in vitro cell models to investigate the molecular mechanisms involved in macrophage activation,’ said the scientist.

From immune response to antibody engineering

Prof. Žvirblienė recalls that the topic of antibodies attracted exceptional interest during the COVID-19 pandemic. Many of us took serological tests to detect coronavirus-specific antibodies, which prompted frequent questions to scientists about the differences between the IgG and IgM antibody classes.

‘B lymphocytes can produce different classes of antibodies depending on the stage of activation. Early in an infection, it is mainly IgM antibodies that are produced ‒ they have limited functionality and only partially protect the body. Upon repeated contact with the antigen, not only does the quality of the antibodies improve, but their class also changes, and their binding to the target antigen becomes stronger,’ explained the researcher.

‘For instance, in the case of an infection, antibodies of IgG class are usually the most beneficial, as they activate various immune cells and neutralise the pathogen. That is why vaccines aim to induce the formation of IgG antibodies,’ added Prof. Žvirblienė.

Antibodies are specialised and adapted to perform different functions. For example, IgA antibodies are secreted in the intestine and the respiratory mucosa, and they are specifically adapted to act and neutralise microbes in such mucous membranes.

‘When developing vaccines, it is crucial to ensure that after vaccination, the necessary class of antibodies will develop that is capable of halting the spread of the pathogen,’ said the Professor.

Antibodies form naturally in our bodies. After an infection or vaccination, each of us develops different classes of antibodies. This is the natural result of the activation of our immune system. In contrast, monoclonal antibodies are created in laboratories – these antibodies are being developed by Prof. Žvirblienė and her team.

‘Back in 1975, new technology enabled the laboratory production of large quantities of antibodies targeting a specific substance. This technology differs from the traditional method employed in the past, where antibodies used to be extracted from blood serum, which always contains a mixture of antibodies – they form in response to various proteins, viruses, and bacteria we have encountered throughout our lives. Now, the hybridoma technology allows scientists to select clones of B lymphocytes (identical cells) that produce monoclonal antibodies of a specific type and with the specificity we need,’ explained the researcher.

By fusing B lymphocytes with tumor cells, scientists can cultivate these hybrid cells in vitro and produce large quantities of specific antibodies.

‘Such monoclonal antibodies can be used for a variety of diagnostic methods and therapies. More efforts are needed to generate therapeutic antibodies. Often, monoclonal antibodies are obtained using B lymphocytes from animals, so they are unsuitable for direct treatment and require additional manipulations to make them more similar to human antibodies. Antibody engineering approaches are exploited to generate recombinant antibodies that can be used to treat cancer or certain inflammatory diseases,’ explicated the Professor.

VU scientists’ catalogue of antibodies

Prof. Žvirblienė and her team have developed monoclonal antibodies against various antigens, such as viral proteins, bacterial toxins, allergens, cytokines, and hormones.

‘We can use these monoclonal antibodies as very specific reagents to detect specific antigens or substances. We have a huge collection of these antibodies,’ noted the researcher.

VU scientists also engage in antibody engineering – for example, using genetic engineering methods to convert a mouse monoclonal antibody into one that closely resembles a human antibody.

‘Such antibodies mimic human antibodies and can be used as positive controls when creating various diagnostic tests. Antibody ‘humanisation’ is also widely applied in developing therapeutic antibodies. However, as a research laboratory, we do not work on this. Competing with large pharmaceutical companies in this area would be extremely difficult,’ said the VU Professor.

The antibodies developed by Prof. Žvirblienė and her colleagues can serve as a valuable molecular tool for further scientific research, as they help investigate the structural features of proteins.

‘When we create antibodies that neutralise a protein’s biological activity and identify which part of the protein the antibody targets, we can study the functional activity of that protein. Combined with other methods, this helps us understand the mechanism of how a protein works,’ explained the scientist.

Prof. Žvirblienė is proud that her laboratory is a member of the European Monoclonal Antibodies Network, known as ‘EuroMabNet’.

‘We joined this network just six years ago and are very happy to be involved in its activities and to share best practices. An important task lies ahead – in 2026, we will host the international ‘EuroMabNet’ conference in Vilnius,’ stated the Professor.

Utilising antibodies to combat diseases

When developing antibodies for therapy, it is extremely important to ensure that they are as similar as possible to human antibodies. This is the only way to ensure that therapeutic antibodies will perform their function and will not cause any side effects.

‘If we would simply took antibodies from a mouse and use them for human treatment, the human immune system would recognise them as foreign and trigger various adverse reactions. That’s why therapeutic antibodies must be identical or as close as possible to human ones. Only then can an effective immune response be achieved without unwanted reactions in the body,’ noted the VU scientist.

Antibodies are used to treat certain autoimmune diseases, such as rheumatoid arthritis. In such cases, therapeutic antibodies neutralise the cytokine that causes inflammation.

‘In patients with rheumatoid arthritis, the body produces too much of an inflammatory cytokine. When antibodies are administered, they neutralise this cytokine, helping to reduce the symptoms of the disease,’ commented Prof. Žvirblienė.

Another critical application of therapeutic antibodies is cancer treatment. One group of cancer-targeting antibodies is designed to inhibit the formation of blood vessels (capillaries). By blocking the development of these blood vessels, it is possible to stop the growth of a tumour. Another way to use antibodies in cancer treatment is to target them against antigens found only on cancer cells.

‘A common problem is that healthy cells may also have such antigens on their surface. In such cases, the antibodies may be ineffective or even activate our immune system to attack healthy cells, leading to unwanted reactions. That’s why developing therapeutic antibodies requires a very lengthy validation process,’ asserted the researcher.

Patented antibodies and financial challenges

Prof. Žvirblienė and her colleagues have patented several antibodies. The scientist emphasises that in order to patent a new antibody, it must not be described in any published articles and must be directed against a completely new target.

‘One of our patented antibodies was developed against a fish allergen, which was extracted for the first time in Lithuania from a local carp. This fish is not found in other countries, so this allergen does not exist there either. Therefore, this particular antibody was, in fact, unique and relatively easy to patent,’ said the researcher.

However, the Professor admits that one of the significant challenges is the high cost of international patents and the lengthy approval process.

‘Every interaction with patent attorneys takes a considerable amount of time, as do the lengthy discussions about the novelty aspects of an antibody, not to mention the cost of the patent application itself that can reach tens of thousands of euro. Later on, patent maintenance fees must be paid, so before filing a patent application, we must carefully weigh up whether the patented antibody can be applied in practice and generate commercial gain,’ she said.

In the business world, the situation is different – the majority of therapeutic antibodies are patented.

‘The pharmaceutical industry involves significant amounts of money, and it is in the interest of companies to protect their developed antibodies for twenty years, as they are motivated to reduce competition. Later, medicines are developed based on these antibodies, generating substantial profits,’ explicated the scientist.

Prof. Žvirblienė notes that many of the antibodies developed by her team have been commercialised – companies now include them in their product catalogues.

‘Such companies pay us licensing fees. These revenues are stable and highly valuable to us because the timing of project calls is unpredictable, and securing project funding is not always easy. Contracts with companies are a great example of how antibodies developed in the laboratory generate real income and provide us, the scientists, with a sense of satisfaction because our knowledge and efforts have been applied in practice,’ concluded the VU Professor.