HARNESSING NATURAL KILLER CELLS FOR CANCER IMMUNOTHERAPY.
AZZAM A. MAGHAZACHI
College of Medicine, University of Sharjah
Natural killer (NK) cells stand at the cross road among treatment of autoimmune diseases and immunodeficient diseases. We reported a new mechanism of action for drugs used to treat multiple sclerosis (MS) patients such as Copaxone (glatiramer acetate or GA; TEVA Inc.). NK cells isolated from patients dosed with GA lysed dendritic cells isolated from the same patients as well killing tumor target cells. Similarly, vitamin D3 or FTY720 (Gilenya; Novartis) augmented IL-2-activated NK cells lysis of tumor cells. We also examined the effects dimethyl fumarate (DMF; Biogen Inc.) and the metabolite monomethyl fumarate (MMF) on various activities of NK cells and demonstrated that MMF induced resting CD56+ NK cell lysis of the NK-sensitive K562 cells and the NK-resistant RAJI cells. Also we demonstrated that GA, MMF and DMF up-regulated the expression of CCR10 on the surface of activated NK cells. This is corroborated with the ability of NK cells to migrate towards the concentration gradients of CCR10 ligands, namely CCL27 and CCL28. These observations were the first to show that drugs used to treat MS can be used to direct the anti-tumor effector cells towards the sites of tumor growth, particularly those secreting the chemokine CCL27 such as melanomas or squamous cell carcinoma, or those secreting CCL28 such as colorectal carcinoma. Hence, drugs used to treat autoimmune diseases can be used to harness NK cells for the purpose of using them in cancer immunotherapy. The present seminar will discuss the results generated during the summer time including observations that further our knowledge on harnessing NK cells for robust therapeutic protocols.