An international research team with strong participation from DTU has developed a new biotechnological platform that makes it possible to test and understand advanced cancer treatments much faster and cheaper than before. The new technology can reduce the development time for new types of cancer immunotherapy from months to days or weeks.
The study, published in the renowned journal Nature Communications, presents a so-called yeast surface display technology that uses modified yeast to mimic human cancer cells. The technology can examine how patients' own immune cells, known as CAR T cells (Chimeric Antigen Receptor), respond to different cancer antigens.
"The most surprising thing for us was how accurately the engineered yeast cells could mimic real cancer cells. They activated CAR T cells almost as effectively as traditional cancer cell lines—and in some cases even more robustly. The combination of precision, speed, and extremely low costs means that we can now test new immunotherapies on a scale and at a speed that simply wasn't possible before. I believe that this platform can help deliver safer and more targeted cancer treatments to cancer patients," says Professor Sine Reker Hadrup from DTU Health Technology.
In the short term, the study will not change specific treatments, but in the longer term, it could have a major impact. The new platform will enable researchers to assess which CAR T variants are most promising much more quickly. CAR T cell therapy is currently most effective against blood cancer. Detailed screening of antigen response can help researchers find entry points to more complex solid tumors, where treatment has traditionally been more difficult.
Recognizes and attacks cancer cells
CAR T cell therapy is a form of immunotherapy in which the patient's own T cells are removed from the body, genetically reprogrammed, and returned to the bloodstream. They are programmed to carry a "CAR" that acts as a targeted sensor that can recognize and attack cancer cells.
It is a potent and often life-saving treatment, especially for blood cancer, but the development of new CAR T therapies is complex, risky, and extremely expensive. Even small differences in cancer antigens from patient to patient can cause the therapy to either work brilliantly—or fail. The goal of the study is to make this development process much more predictable.
Modified yeast cells used to test immunotherapy
The researchers have genetically modified common yeast strains so that they can express human cancer antigens on their cell surface. This means that the surface of the yeast acts as a kind of biological test screen, where the recipe for a specific cancer antigen is inserted into the yeast cell. The yeast strain produces and displays this antigen on its outer surface, almost as if it were a cancer cell, and researchers can then expose the yeast strains to CAR T cells and measure how they respond.
The method is much cheaper and faster than growing human cancer cells or using advanced nanotechnological systems. The researchers behind the study emphasize that the yeast-based models work just as well as - and in some cases more robustly than—traditional cancer cell lines.
Faster and more precise cancer treatment
According to DTU researchers Professor Sine R. Hadrup, Marcus Deichmann, and Emil D. Jensen, the platform makes it possible to test many different antigens quickly and systematically and to better understand why certain CAR T designs work better than others. In addition, the platform makes it possible to test and predict how CAR T cells respond to the various strategies that cancer cells use as a 'shield' against the immune system. This means that new, improved CAR T therapies can be developed much faster.
What is particularly remarkable is that yeast grows extremely quickly and can be adapted in just a few days. This makes the new technology a flexible screening tool that all research environments - large and small - can benefit from.
