Antibody engineering based on gene technology is the key research area of the research group led by Urpo Lamminmäki, Professor of Biotechnology and Group Director at InFLAMES. While biologists identify and research things that already exist, the Lamminmäki group creates something that does not exist yet.

“We conduct a lot of applied research. We are developing, among other things, new methods and tools for the production of antibodies and applying them to the production of antibodies tailored for a specific purpose,” says Urpo Lamminmäki in his room in Medisiina D. We are at the University of Turku’s Department of Life Technologies.

Lamminmäki says that his group’s work is very different from basic biological research.

“If biologists are like explorers looking for something that already exists and finding an explanation for the discovery, we are perhaps more like engineers because we are trying to create something that does not exist yet.”

Antibodies have a long history

The Lamminmäki group creates antibodies. They are proteins that recognise and bind to substances harmful to the body, such as viruses or bacteria, and help the body fight them.

The history of antibodies is long. Even before their biology was fully understood, they were used to prevent diseases. In his Professorial Inaugural Lecture, Lamminmäki explained that in the 1880s, researchers discovered that transferring blood from an animal inoculated with toxins produced by bacteria to an uninoculated animal protected the latter from bacterial infection. Based on the research findings, the production of a diphtheria medicine was started using a method in which a serum to prevent the disease was isolated from the blood of horses inoculated with diphtheria toxin.

The precise structure and binding mechanism of antibodies were discovered in the 1960s, and it was only during the next decade that a deep understanding emerged regarding the genetic mechanisms that produce antibody diversity.

An antibody library can offer billions of options

The functions of the immune system determine the properties of naturally produced antibodies, which can complicate the development of an antibody suitable for a particular biotechnical or medical application.  In addition, this involves animal testing, a phenomenon that the scientific world is trying to eliminate. Modern science’s solution to these problems is gene technology and the artificial antibodies that can be created with it. The resulting antibody libraries are collections of different antibodies or parts of them. There are millions or even billions of them in these collections.

“We have been developing such antibody libraries for some time now, and we are currently working on improving the libraries that we have already created. In this way, they can be used to find completely new types of solutions that work in the development of more complex biopharmaceuticals, for example,” says Urpo Lamminmäki.

Antibody libraries are also used in the development of diagnostics and are, on the whole, important “toolkits” for biological and medical research.

Biopharmaceuticals are antibodies

Antibody-based biopharmaceuticals have revolutionised the treatment of many diseases. A good example is rheumatic diseases, in which the disease can be brought to complete remission with medication.

The development of biopharmaceuticals requires comprehensive design and engineering of the antibody structure to achieve the desired functionalities and properties. In addition to good specificity and strong binding capacity, many other properties are required of medical antibodies. 

“In our field, there is a lot of talk about so-called developability, or potential for development, which is an estimate of how reliably a pharmaceutical molecule candidate behaves or how likely it is to become a working pharmaceutical. This depends on many of the chemical and physical properties of the antibody.”

“Let’s assume that we have an antibody molecule that looks biologically interesting, in other words, it has an inhibitory effect on the biological function we want. However, this does not necessarily mean it is suitable for pharmaceutical use. Furthermore, it needs to be a molecule that does not coagulate easily even at high concentrations, for example. It must also be able to withstand storage and be produced and dosed in a sensible manner. Efforts can be made to solve these issues already when building an antibody library: we try to ensure that there are molecules in the library that would be as suitable as possible for being turned into pharmaceuticals.”

So, who is it that needs new antibodies and antibody libraries? They are needed by long-term research groups and companies with ongoing product development processes. The Lamminmäki Antibody Engineering Group is co-operating with both the academic and the business world. The group consists of 13 researchers.

Liisa Koivula