Researchers at Lund University have developed a new method to reprogram easily accessible cells into rare immune cells, aiming to improve treatments for diseases such as cancer. The team has created a library containing over 400 factors that are involved in immune cell identity and function, which serves as the foundation for identifying the combinations needed to generate specific types of immune cells.
Ilia Kurochkin, postdoctoral researcher at Lund University and first author of the study, explained the significance of immunotherapy: "Immunotherapy is a group of treatments that help the body defend itself by strengthening or controlling the immune system. In cancer, current approaches include, for example, CAR-T cell therapy, where a patient's own T cells are genetically modified to better find and kill cancer cells. It is one of the most promising methods in modern medicine."
Kurochkin noted that while immunotherapies have shown promise, not all patients respond to existing treatments. One challenge is that many crucial immune cells are rare and difficult to obtain from blood samples. He said: "However, progress has been limited because we still do not fully understand the factors that control the identity and function of cells. To convert a more accessible cell – for example, a skin cell – into a specific immune cell, we first need to know which factors are needed for reprogramming and generate that particular identity."
To address this challenge, researchers labeled each factor in their library with unique DNA barcodes. This approach allowed them to test thousands of combinations at once and track which combinations successfully transformed common cells into specific immune cell types.
Filipe Pereira, Professor of Molecular Medicine at Lund University who led the study, described their achievement: "It took us four years to develop the screening technique and complete the library. This is the foundation for subsequently creating 'recipes' for reprogramming immune cells. Depending on the type of cell you want to reprogram that can be harnessed to treat multiple diseases, you go to the 'recipe book' to see the instructions for reprogramming."
The platform has already enabled researchers to identify recipes for six different types of immune cells and made it possible—according to their report—for the first time through reprogramming methods to produce previously inaccessible types such as natural killer (NK) cells. NK cells play an important role in fighting cancer.
The research team plans further work using this technology with other diseases involving malfunctioning or missing immune responses.
Immune cellular reprogramming remains an emerging field; until now scientists had mapped key factors only for four out of more than 70 human immune cell types. The new library from Lund University aims to accelerate discovery in this area by providing tools necessary for large-scale generation of diverse functional immune cells.
