Journal: International Journal of Molecular Sciences
Article Title: Leveraging Natural Killer Cell Innate Immunity against Hematologic Malignancies: From Stem Cell Transplant to Adoptive Transfer and Beyond
doi: 10.3390/ijms24010204
Figure Lengend Snippet: Strategies to promote anti-tumor effector function for NK cell immunotherapy. (1) NK cell engagers include bispecific (BiKEs) and trispecific antibodies (TRiKEs) that bring tumor antigens and supportive cytokines into proximity with NK cell receptors. (2) Supportive cytokine-mediated approaches include the use of IL-2 and IL-15 to promote NK cell expansion and cytotoxicity. (3) Impairing TGF-β signaling and preventing buildup of adenosine in the tumor microenvironment can reduce local suppressive effects on NK cells. (4) Blockade of immune checkpoints (PD-1, PD-L1, CTLA4) and inhibitory NK receptors (KIR2D) may circumvent NK exhaustion and improve anti-tumor function. (5) The addition of monoclonal antibodies and engineering of high affinity CD16 receptors promote the CD16-Fc ligand binding interaction, leading to enhanced ADCC. (6) Engineered selective antigen receptors such as CARs and TCRs can redirect NK cells towards specified tumor antigens and increase cytotoxicity. NK: natural killer, BiKE: bispecific killer engagers, TRiKE: trispecific killer engagers, Ag: antigen, NKG2D: natural killer group 2 member D, IL: interleukin, TGF-β: transforming growth factor beta, AMP: adenosine monophosphate, PD-1: programmed cell death protein 1, CTLA-4: cytotoxic T-lymphocyte associated protein 4, KIR2D: killer immunoglobulin-like receptor group 2 member D; PD-L1: programmed death-ligand 1, ADCC: antibody-dependent cellular cytotoxicity, TCR: T cell receptor, CAR: chimeric antigen receptor. Created with BioRender.
Article Snippet: I/II , Biohaven Pharmaceuticals , Autologous memory-like NK cells with BHV-1100 (antibody recruiting molecule) and low-dose IL-2 , MM , NCT04634435.
Techniques: Ligand Binding Assay
