Adoptive T cell therapy, a treatment that uses a patient’s own immune cells to fight cancer, has shown remarkable success in some blood cancers and has the potential to transform cancer care. However, in most solid tumors, these therapies are far less effective. One major challenge is that the transferred T cells often lose strength and persistence after entering the body because they do not receive enough of the immune-supporting signals they need to survive and continue attacking cancer.
One of the most important of these signals is a natural immune protein called interleukin-2 (IL-2), which helps T cells grow and remain active. While IL-2 can be given as a drug, it spreads throughout the entire body, stimulating many immune cells indiscriminately and causing severe, sometimes life-threatening side effects.
Dr. Hinrichs’ research seeks a safer way to provide this critical support only to the therapeutic T cells. His project introduces an innovative solution: a built-in “on-demand” support system engineered directly into the cancer-fighting T cells. He and his team have created a molecular switch, called a “ligaceptor,” that stays inactive until triggered by a small-molecule drug. Once activated, the switch delivers IL-2-like support specifically inside the engineered T cells, helping them expand and persist without overstimulating the rest of the immune system. Early studies have already shown strong and controllable effects in human T cells.
Dr. Hinrichs will now test this approach in tumor models and develop additional switches that deliver other supportive signals. If successful, this work could make T cell therapies safer, more precise, and more effective for patients with solid tumors.
Project and Grants
On-demand cytokine support to enhance adoptive T cell therapy
