Kira Gritsman, MD, PhD

Waking up the immune system to kill tumor cells has become an effective way to treat some types of cancer. Unfortunately, this does not work well for acute myeloid leukemia (AML), a lethal type of blood cancer. This is because leukemic cells have found ways to put T cells to sleep. New strategies are needed to re-awaken T cells, an important component of the immune system, to help them kill leukemic cells. The protein PI3 kinase (PI3K) delta is found both in leukemic cells and in T cells. When PI3K delta is blocked, this can activate T cells in mice or in cancer patients. We found that loss of PI3K delta in leukemic mice improves survival by activating T cells. We are testing a new drug that blocks PI3K delta and activates T cells in cancer patients without causing many side effects. We found that treatment of leukemic mice with this drug can also activate T cells. The drug venetoclax is frequently used to treat leukemia patients, but some patients relapse. We will test whether adding the PI3K inhibitor to venetoclax could kill more leukemic cells than venetoclax alone by activating T cells to kill leukemic cells. If this treatment effective in leukemic mice and in a culture dish, then we will design a clinical trial to test this drug combination in leukemia patients.