Grants - Translational Grants - Missouri - 2017

Todd Fehniger, Ph.D., M.D.

Most patients with acute myeloid leukemia (AML) have a poor prognosis, and a “bone marrow” or hematopoietic cell transplant (HCT) is the only chance for a cure. The new immune system that develops in the patient is the active part of the therapy, including natural killer (NK) cells. A major obstacle for HCT in AML patients are the complications that occur due to high doses of chemotherapy. Newer transplant types referred to as “mini” transplants are more tolerable with fewer side effects, but have a high relapse chance. We developed a new method to activate donor NK cells, which result in a long-lived, highly potent memory-like NK cell. These are made from donor immune cells by purifying the NK cells, activating overnight cytokines, and then infusion into the patient. This new NK cell therapy approach has been tested in a phase 1 study at WUSM for patients with AML with promising clinical results and no major side effects.  However, without a “matched” immune system, the AML patient’s immune cells reject the donor NK cells after 2-3 weeks, and thus the memory-like NK cells have only a few week “window of opportunity” to eliminate the AML.  Here, we combine the “mini” HCT transplant with memory-like NK cell infusion from the same donor to leverage the strengths of each individual approach.  We expect that the donor memory-like NK cells will result in a complete remission, allowing time for the new immune system to develop and safely provide a long term cure.

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