The immunosuppressant agent daclizumab, which is used to prevent acute organ rejection in persons undergoing renal transplants, has now been shown to improve survival by 30% in patients with breast cancer who received a therapeutic vaccine.
Robert H. Vonderheide, MD, DPhil, and James Riley, PhD, both of the Perelman School of Medicine of the University of Pennsylvania in Philadelphia, led a team that theorized daclizumab could effectively deplete regulatory T cells (Tregs) and restore the immune system’s ability to fight tumors. As the investigators wrote in Science Translational Medicine (2012;4:134ra62), Tregs are key mediators of immune tolerance and feature prominently in cancer. Tumor cells draw Tregs to the tumor area, where the Tregs rely on the protein IL-2 for most of their functions.
Daclizumab is a monoclonal antibody that binds to the CD25 receptor on the surfaces of Tregs, depriving the cells of IL-2. The lack of IL-2 forces Tregs to convert into normal T cells that no longer surround the tumor, allowing immune cells to make their way in to battle the tumor.
To learn more about the impact of daclizumab on Tregs in humans, Vonderheide, Riley, and colleagues performed a clinical trial of daclizumab in combination with an experimental cancer vaccine being developed at their facility. Among the 10 study participants, all of whom had metastatic breast cancer, the agent worked “incredibly well,” said Vonderheide in an announcement from the medical school: The T-cell conversion lasted 2 months and no side effects were detected. Although the tumors did not shrink, they did stop growing in six of the patients. The patients receiving the vaccine plus daclizumab survived about 7 months longer than those given vaccine only.
Because Tregs can block the immune response against most human cancers, “Drugs like daclizumab might be useful for most cancer patients, especially those receiving other types of immune therapy,” noted Vonderheide.