Enhancing Natural Killer Cell Stimulation and Specificity to Acute Myeloid Leukemia
Mentor: Challice Bonifant
The goal of our laboratory is to develop cell-based immunotherapy to target acute myeloid leukemia (AML). Natural Killer (NK) cell immunotherapy is especially pertinent to the treatment of AML, as myeloid leukemias have been identified as expressing NK cell activating ligands (Mastaglio et al., 2018). NK cell transfer to AML patients has been shown to be safe and has demonstrated anti-tumor activity (Knorr et al., 2014). However, effective induction and maintenance of anti-AML immunity requires transfer of large numbers of NK cells. Procurement of the necessary dose from patients has proven challenging (Ullah et al., 2016). It should be noted that NK cells do not cause graft-versus-host disease (GVHD), a severe toxicity seen with allogenic T cell transfer (Simonetta et al., 2017). Because of this, donor cells can be used to manufacture an AML-specific cellular therapy product. Finally, while NK cells are themselves cytotoxic to leukemia, they may be made more powerful and specific. NK cells can be genetically engineered resulting in greater in vitro proliferation and cytotoxicity (Shimasaki et al., 2016), precisely what is required to combat AML. The initial goal of this project is to develop a more effective way to proliferate NK cells in vitro, in order to increase the number of cells available for transfer to patients. We then plan to enhance NK cell anti-AML cytoxicity through genetic modification.
