Project Term: July 1, 2018 - June 30, 2022
We propose to develop a novel personalized immunotherapy to treat patients with refractory acute myeloid leukemia. We have shown that tumor-specific T cells (TAA-T) can diminish leukemia disease burden after allogeneic stem cell transplant. We now propose to augment the efficacy of the TAA-T products in the autologous setting using IL-15 backpacks to enhance TAA-T function and enhance efficacy without increased toxicity in vivo.
This project will test a novel immune therapy to treat patients with relapsed or persistent acute myeloid leukemia (AML). Patients with acute myeloid leukemia who fail to achieve remission with chemotherapy have few treatment options, especially if their disease cannot be controlled well enough to proceed to blood and marrow transplantation—the only known cure. While chimeric antigen receptor T cell (CAR-T) therapy has been shown to successfully treat acute lymphoblastic leukemia (ALL), it has not been effective for those suffering from AML. We developed a therapy (TAA-T) designed to target and kill leukemia cells while having little or no effects on nearby healthy cells. Such treatments are a substantial improvement over other immune therapies (CAR-T, for example) that inflict harmful toxic effects such as fluid leaking into the lungs requiring ventilation or intensive care to support the blood pressure. In our previous work, we demonstrated that TAA-T, administered after allogeneic hematopoietic cell transplantation (HCT), cleared leukemia in 71% of patients who had exhausted all other treatment options. We now propose to enhance the activity of TAA-T to treat patients with relapsed or persistent AML before transplantation. We have partnered with Torque Pharmaceuticals, which developed a novel technology to attach a “backpack” of immune-enhancing elements to the TAA-T cells. The backpack only activates T cells that have been exposed to leukemia, sparing the patient from experiencing the devastating symptoms of overwhelming inflammation that are seen with other immunotherapies like CAR-T. Moreover, TAA-T targets several tumor-specific proteins, making it less likely for the tumor to escape the immune attack by hiding a single molecule (a limitation of CAR-T therapy). We therefore hypothesize that backpacked TAA-T will effectively kill leukemia in patients with relapsed or persistent AML. We propose to test this hypothesis by 1) Manufacturing and characterizing the backpacked TAA-T cell product in the laboratory, 2) Treating patients with “backpacked” TAA-T to determine the safety and efficacy of this therapy to kill the leukemia cells in patients with persistent disease, and 3) Studying the blood of the patients to track the persistence and efficacy of the treatment. If backpacked TAA-T is found to be a therapeutic success for these patients, it would result in a dramatic improvement of outcomes for patients with little hope of survival.