The Knut and Alice Wallenberg Foundation has granted SEK 835 million to 30 different projects in medicine, natural science and technology that are deemed to have the potential to pave the way for future scientific breakthroughs. The foundation uses a peer-review procedure where the applications are evaluated by leading international experts in the respective fields. Three research projects were awarded grants at Lund University, two of which at the Faculty of Medicine.
Memory cells control long-term immunity
Joan Yuan wants to investigate how our immunological memory is formed. She hopes that this will generate knowledge about how we could optimise the immune system and develop better vaccination strategies.
Our B cells create an immunological long-term memory after an infection or vaccination. This forms the basis of long-term immune system defense.
"These cells remember the foreign substance, which allows the body to react faster and stronger if it is exposed to the same substance in the future," says Joan Yuan, associate professor of immunology and research group leader at Lund Stem Cell Center.
The memory B cells are formed during different stages after exposure to a foreign substance and are programmed for different properties. But knowledge about the various subgroups is largely unexplored. Therefore, a more comprehensive understanding of the complexity of our immunological memory bank is needed, in order to best fight infections. Another aspect is being able to develop strategies to ensure that future vaccines also protect against mutated variants of bacteria and viruses.
"By labeling - in mice - different subgroups of memory B cells with distinct fluorescent proteins, we can distinguish and follow them throughout life to see which immune reactions they contribute to and how they differ from other immune cells."
Joan Yuan's research group, together with co-investigating groups at the Karolinska Institutet and the University of Gothenburg, have identified three factors that can be decisive for how the emergence and function of memory B cells is controlled. In part, it depends on whether the cells are formed early or late in the process after an infection or vaccination, but also where in the body they are created and stored, as well as the role of pre-existing memory B cells that are formed early in life.
"Our goal is to provide a deeper understanding of which mechanisms control the immune system's memory bank and, by extension, how we can use this knowledge for better vaccination strategies," says Joan Yuan.
Reprogramming reveals tumor cells
Filipe Pereira bases the next generation of immunotherapies on reprogramming the cancer cells into immune cells. He wants to use the tumor-specific antigens to increase the effectiveness of cancer immunotherapies.
Every time cancer cells mutate, new antigens are produced, so-called neoantigens, which are presented on the surface of the cancer cell. These are presented on the surface of the cancer cell and differ from the protein of healthy cells. Our T cells, which are part of the immune system, can identify these neoantigens as potentially harmful and therefore eliminate the cells that carry them. Cancer immunotherapy harnesses the ability of T cells by stimulating our immune system with vaccines or neoantigen-specific T cell therapies.
"But in some cases, the immune system's methods are ineffective when it comes to identifying the tumor-specific antigens. Cancer cells are very adaptable and can develop mechanisms to avoid detection by the immune system," says Filipe Pereira, professor of molecular medicine at Lund University, and research group leader at Lund Stem Cell Center.
Because the cancer cells consistently try to avoid being recognized by the T cells, the researchers want to develop new strategies to outwit and expose them. They base the next generation of cancer immunotherapies on reprogramming the cancer cells. With the help of three molecules, so-called transcription factors, they can in just over a week convert the cancer cells into immune cells and then force them to present the neoantigens on their surface. In this way, a new treatment concept against cancer can be obtained.
"We have two goals. Partly to test the identified neoantigens in cancer vaccines and partly to create a platform for T-cell treatments that are specific for neoantigens and thus increase the effectiveness of cancer immunotherapies," says Filipe Pereira.
