Elucidating Programs of an Effective Natural Killer Cell Therapy

Dr. Foltz is focused on Natural Killer (NK) cells, a part of the immune system that can be a very safe and effective cancer killer.  Unlike other donor cells, NK cells can be administered to a patient in a short amount of time from unrelated donors, with much less risk to the patient. In contrast to T cells, NK cell killing is antigen non-specific, instead NK cells rely on a balance of signals through numerous activating and inhibitory receptors that tip a NK cell towards either tolerance or target cell killing. NK cells can become even better at destroying cancer by being “educated” using particular cytokines to create “memory-like” ML NK cells.  These ML NK cells can double the clinical response expected from conventional NK cells and are extremely safe. Further, ML NK cells can persist for at least 2 months in leukemia patients, extending potential therapeutic response. Dr. Foltz recently uncovered that not all ML NK cells are equal and that, when activated with cytokines, some ML NKs become enriched, and that the enriched ML NK can be divided into two groups, with differing levels of efficacy. 

Dr. Foltz posits that not all NK donors are equal and that bioinformatic inquiry may allow doctors to identify which donors will produce more enriched ML NK cells.  With her CRF Young Investigator Award, Dr. Foltz will attempt to map out the molecular landscape that leads to the development of an enriched ML NK cell that is capable of eliminating leukemia. Additionally, Dr. Foltz envisions applying this data analysis and tool development across multiple leukemia trials in the future to see if the types of ML NK found in the samples correlate with patient response.  In a related aim, Dr. Foltz will focus on a particular transcription factor which she hypothesizes promotes the enhanced ML NK leukemia response. Taken together, the possibility that donors might be selected for their high potential of ML NK cells and the evidence of a factor that could enhance more NK cells could create a whole new avenue for cellular therapy for leukemia patients.