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Creative biolabs.cart nk cell-based-therapeutics
- 1. © 2007 - 2019 Creative-Biolabs All Rights Reserved Email: info@creative-biolabs.com Tel: 1-631-381-2994 NK CELL-BASED THERAPEUTICS Products: Diseases Associated Antigen CAR Vector System Viral Particle CAR/TCR Development Kits One-Stop CAR-T Therapy Development Services CAR Modified NK Cell Development Services TCR Modified T Cell Development Services Dendritic Cell Vaccine Development Services Bispecific TCR & TCR-Like Antibody Services WHAT WE DO: Adoptive transfer of NK cells without genetic engineering1 Autologous NK cell transfer Autologous transfer of CAR-NK cell Structural and functional basis of CAR Adoptive transfer of NK cells with CAR modification2 NK cell-mediated molecular therapeutics3 In autologous transfer, natural killer (NK) cells from the patient are activated and expanded in vitro in the presence of cytokines. Feeder cellsare often used. The expanded and activated NK cells are then transferred back into the patient, who generally receives cytokine administra- tion to sustain the expansion and function of the infused NK cells. Although autologous NK cells might recognize activat- ing signals such as stress molecules on cancer cells, their anti-tumor activity is limited by the inhibitory signal transmitted by self HLA mole- cules. In allogeneic transfer, NK cells can be obtained from HLA-matched or haploidenti- cal donors. NK cells are expanded but T cells should be removed to avoid GVHD. In this setting, the best respons- es are obtained when haploidentical donors do not express KIRs that recognize the patient’s HLA molecules. Chimeric antigen receptors (CARs) can be engineered in autologous or allogeneic NK cells or in NK cell lines. CARs are designed by the fusion an antigen-binding domain with a hinge region, a transmem- brane domain and one or more stimulatory molecules. In addition to adoptive trans- fer, NK cells are also involved in molecular based therapies. Stimulatory cytokines, small molecule activators/inhibitors, monoclonal antibodies (mAbs) including bispecific antibodies (bsAbs), and antibody-drug conjugates (ADCs) are utilized to target inhibitory/activating receptors/ligands, tumor antigens, immuno-suppres- sive molecules, and the tumor microenvironment, to improve the anti-tumor activity of NK cells. Creative Biolabs Cellular Therapy Solutions CAR vectors CAR-NK cells Monocytes Monocytes NK cells Monocytes NK cells NK cells Tumor antigenTumor cell Antigen-binding region (scFv) VH VL Hinge region Transmembrane region Signal transduction region NK cell Tumor cell Mismatch Tumor cell Patient KIR NK cell Patient HLA + – Match Donor KIR NK cell + Treatment with stimulatory cytokines • IL-2 IL-15 IL-12 IL-18• • • Inhibitory Activating Targeting NK cell receptors • KIR2DL NKG2A PD-1 LAG3 TIGIT TIM3 GITR 4-1BB • • • • CD70 CD27 SLAMF7• • • • • • Targeting the tumor microenvironment • PDL1 TGFβ IDO CD39 CD73 C5aR MICA MICB • • • • • • • Targeting tumor antigens • SLAMF7 CD27 EGFR CD70 NKp46 B7-H6 MICA MICB CD30-CD16 CD33-CD16 EGFR-CD16 • • • • • • • • • • Allogeneic NK cell transfer Patient Patient Patient Donor Tumor cell NK cell Block inhibitory NK receptor Stimulate activating NK receptor Masking inhibitory ligands Neutralize immuno- suppressive molecules Induce ADCC ADC bsAb-mediated conjugation CD16 + + Treg cell MDSC ––