NK-Cell-Based-Therapeutics

NK CELL-BASED THERAPEUTICS In autologous transfer, natural 1 Adoptive transfer of NK cells without genetic engineering killer (NK) cells from the patient are activated and Autologous NK cell transfer Allogeneic NK cell transfer expanded in vitro in the presence of cytokines. Feeder Patient NK NK Donor cellsare often used. The cell cell expanded and activated NK + + cells are then transferred back Patient KIR into the patient, who generally – Donor KIR Monocytes receives cytokine administra- tion to sustain the expansion Match and function of the infused NK Mismatch cells. Although autologous NK cells might recognize activat- Patient HLA Patient ing signals such as stress molecules on cancer cells, Tumor cell Tumor cell their anti-tumor activity is limited by the inhibitory signal Monocytes NK cells NK cells transmitted by self HLA mole- cules. In allogeneic transfer, 2 Adoptive transfer of NK cells with CAR modification NK cells can be obtained from HLA-matched or haploidenti- Autologous transfer of CAR-NK cell Structural and functional basis of CAR cal donors. NK cells are expanded but T cells should Patient NK VL be removed to avoid GVHD. In cell Antigen-binding this setting, the best respons- es are obtained when VH region (scFv) haploidentical donors do not express KIRs that recognize Hinge region the patient’s HLA molecules. Chimeric antigen receptors CAR-NK cells Transmembrane (CARs) can be engineered in CAR region autologous or allogeneic NK vectors cells or in NK cell lines. CARs are designed by the fusion an Tumor Signal transduction antigen-binding domain with a Tumor cell antigen region hinge region, a transmem- brane domain and one or Monocytes NK cells more stimulatory molecules. 3 NK cell-mediated molecular therapeutics Stimulate bsAb-mediated activating conjugation NK receptor Treatment with ADC Targeting the tumor stimulatory cytokines ++ microenvironment NK • IL-2 • IL-15 cell • PDL1 • TGFβ • IL-12 • IL-18 –– • IDO • CD39 • CD73 • C5aR In addition to adoptive trans- Induce Tumor cell • MICA • MICB ADCC fer, NK cells are also involved in molecular based therapies. Stimulatory cytokines, small Targeting NK cell receptors molecule activators/inhibitors, CD16 Targeting tumor Inhibitory Block inhibitory antigens monoclonal antibodies (mAbs) NK receptor Neutralize • SLAMF7 • CD27 • KIR2DL • NKG2A immuno- • EGFR • CD70 including bispecific antibodies • PD-1 • LAG3 suppressive • NKp46 • B7-H6 • TIGIT • TIM3 molecules • MICA • MICB (bsAbs), and antibody-drug • GITR • 4-1BB • CD30-CD16 • CD33-CD16 conjugates (ADCs) are utilized • EGFR-CD16 to target inhibitory/activating Activating receptors/ligands, tumor • CD70 • CD27 Treg cell • SLAMF7 antigens, immuno-suppres- MDSC sive molecules, and the tumor Masking inhibitory ligands microenvironment, to improve the anti-tumor activity of NK WHAT WE DO: cells. Creative Biolabs One-Stop CAR-T Therapy Development Services Products: Cellular Therapy CAR Modified NK Cell Development Services Diseases Associated Antigen Solutions TCR Modified T Cell Development Services CAR Vector System Dendritic Cell Vaccine Development Services Viral Particle Bispecific TCR & TCR-Like Antibody Services CAR/TCR Development Kits Copyright © 2018 Creative Biolabs. All Rights Reserved. | Contact Us