β-Hydroxybutyrate To Enhance CAR T Cell Immunotherapy Against Hematological Cancers

CAR T-cell therapy is a groundbreaking treatment for blood cancers such as leukemia and lymphoma. It works by using the patient’s own immune cells, which are modified in the lab to better recognize and attack cancer cells. While this therapy has been life-saving for some patients, many still relapse, or the treatment does not work as well as hoped. One of the reasons for this is that CAR T cells often lose energy and become exhausted when they are inside the body, especially in the tough environment created by cancer. As a result, these cells struggle to survive and fight the cancer effectively.

Our research focuses on improving CAR T-cell therapy by using a special diet known as the ketogenic diet. This diet causes the body to produce a substance called beta-hydroxybutyrate (BHB), which is a type of fuel that cells can use. We believe that BHB can help CAR T cells stay energized and function better in fighting cancer. Our early research shows that BHB helps CAR T cells by improving their ability to produce energy, survive longer, and kill cancer cells more effectively.

In this project, we will test whether giving BHB directly to CAR T cells can improve their function for treating different types of blood cancers. First, we will use animal models of cancers like B-cell and T-cell lymphoma, multiple myeloma and acute myeloid leukemia to see if BHB can help CAR T cells work better in different blood cancers. If we see improvements in these models, it could mean that BHB has the potential to make CAR T-cell therapy more effective for many types of blood cancer patients.

We will also test BHB in healthy human donors to understand how it affects their T cells, which are similar to the CAR T cells used in therapy. By studying these effects in healthy people, we hope to learn how best to use BHB to boost the effectiveness of CAR T-cell therapy in cancer patients.

If successful, this research could lead to a new, safe, and easy-to-implement strategy for improving CAR T-cell therapy by simply using a special type of fuel (BHB) to keep the cells energized and effective. This could make CAR T-cell therapy a more powerful option for treating blood cancers, offering hope to patients who currently do not respond well to the treatment or who experience a relapse. By enhancing the body’s own immune response, we hope to make long-lasting remissions a reality for more blood cancer patients.