For around 20 years, so-called therapeutic antibodies produced artificially in the laboratory have been increasingly used in the treatment of cancer, autoimmune diseases – and recently also SARS-CoV-2. The Tyrolean chemist Klaus Liedl is working with his 30-person group at the University of Innsbruck on the optimal design of these therapeutic antibodies. Fragments of shark and camel antibodies are also used, he described in an APA interview.
Antibodies are a central part of the human immune system. The purpose of the proteins is to trap antigens or damaged cells that have penetrated them, preventing them from interacting with the cells of the body or from entering the cells. This central function of antibodies has inspired pharmaceutical research to develop so-called therapeutic antibodies using molecular biological methods.
However, these are much larger than molecules that are ingested via tablets – which has advantages and disadvantages, as Liedl explained: “At several weeks, they stay in the body and therefore last much longer than traditional drugs made from small chemical compounds “. These often only lasted a few hours.
In addition, according to Liedl, the therapeutic antibodies can be produced relatively easily for use in a wide variety of diseases thanks to the molecular biological selection. “The building blocks of the antibodies can be combined like Lego blocks,” he said. Since antibodies are proteins, they also contain no toxic components, according to the university professor who conducts research at the Innsbruck Institute for General, Inorganic and Theoretical Chemistry.
However, due to their size, therapeutic antibodies cannot be taken orally and must be injected. Otherwise they would simply be digested, noted Liedl. “So far, therapeutic antibodies have been developed for diseases whose points of attack are on the cell surface – which are easily accessible for the antibodies,” the scientist explained. In order to expand the range of treatments, the antibodies would also have to be able to penetrate the cell or the central nervous system. This is where camels and sharks come into play. Because the binding regions of their antibodies are much more compact than the human ones.
Following their example, Liedl and his team design so-called nanobodies: “We use the upper part of the shark or camel antibodies, i.e. their much smaller ‘binding interface’ – and use this on human antibodies that have been modified in terms of molecular biology, which then facilitate further communication take over with the cells, the chemist described.
The core expertise of his working group lies in researching the specificity of antibodies, Liedl specified. “In response to antigens, our immune system produces ever more specific, ever stronger binding antibodies. That makes sense, of course, but becomes a problem when mutations occur,” explained Liedl, referring to coronavirus mutants. He and his team would aim to “understand how specific the antibodies are and what to do to precisely modulate that specificity”.
At the moment, production and treatment costs are still very high, but due to the precise design and good tolerability, the advantages of therapeutic antibodies outweigh the benefits, explained Liedl. The pharmaceutical industry now makes the same turnover with biologicals – mostly therapeutic antibodies – as with conventional drugs. “Conventional small molecules also have their strengths, but the pharmaceutical industry can currently reap a lot of low-hanging fruit with biologics,” said Liedl, referring to a steep learning curve and many new opportunities that had opened up in the recent past. “There is still a lot of room for new developments here”. However, according to the researcher, therapeutic antibodies would not completely replace conventional drugs.