Ryan Friess

Natural Killer cells are an innate immune cells ideal traits for cancer immunotherapy, but proliferating Natural Killer cells with the cytokine IL-15 leads to the downregulation of activity through the metalloprotease ADAM17. Blocking ADAM17 activity is a potential solution, with this study using a bispecific fused scFv to target both ADAM17 and the Natural Killer cell marker CD16. Lymphocytes were labeled with a cell dye to track proliferation and were then treated with IL-15 and various concentrations of the TAB16 bispecific scFv and the ADAM17 antibody MEDI3622. It was found that TAB16 had increased proliferation at lower concentrations than MEDI, suggesting increased potency. It also maintained CD16, an ADAM17 substrate and an essential receptor for antibody killing, better than MEDI. When ADAM17 activity was upregulated, it cleaved the receptor CD62L on both NK cells and T cells. MEDI provided protection from this effect to both NK and T cells, but TAB16 only protected NK cells. This suggests that TAB16 works as a more potent blocking agent of ADAM17 activity for NK cells specifically, with increased proliferation and receptor maintenance, opening the way for use in vivo and for cancer cytotoxicity.