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TNFR Superfamily Co-Stimulatory Receptors

TNFRSF Co-Stimulatory Receptors as Immune Checkpoint Targets

In contrast to blocking inhibitory immune checkpoint receptors to improve anti-tumor immune responses, researchers are also looking at using agonists of co-stimulatory immune checkpoint receptors. The majority of these co-stimulatory receptors are members of the tumor necrosis factor receptor superfamily (TNFRSF). They are primarily expressed on the surface of T cells, B cells, and/or natural killer (NK) cells and upon activation, with either their ligands or agonistic antibodies, they promote signaling pathways that enhance the survival, proliferation, and effector functions of these cells. The anti-tumor effects of stimulating these receptors alone, or in combination with antibodies that block inhibitory receptors like CTLA-4 or PD-1, are being actively explored. Details about the primary TNFRSF co-stimulatory molecules that are currently being investigated as immuno-oncology targets are described in the sections below.

Bio-Techne offers R&D SystemsTM bioactive recombinant proteins for all of the co-stimulatory TNF receptor superfamily members that are being investigated as immuno-oncology targets, and their ligands. Our portfolio includes proteins for a variety of different species with different tags including an expanding selection of Avi-tag biotinylated proteins. Additionally, we offer a wide selection of antibodies against these targets that are validated for a range of applications to help advance our understanding of the immune-stimulatory functions of these molecules.

TNF Receptor Superfamily Members Can Promote T Cell and Natural Killer Cell Activation

TNF receptor superfamily co-stimulatory immune checkpoint targets that are being investigated as immuno-oncology targets.

Activation of immune cell co-stimulatory receptors belonging to the TNF receptor superfamily is another strategy being investigated for cancer immunotherapy. As an alternative to blocking inhibitory immune checkpoint receptors to restore antitumor immune responses, agonists of co-stimulatory immune checkpoint receptors are also being explored. Many of these co-stimulatory receptors belong to the TNF receptor superfamily and have been shown to be involved in enhancing the proliferation and effector functions of T cells and/or natural killer (NK) cells, while some also inhibit the activity of regulatory T cells.

Analysis of the Binding of R&D Systems Recombinant Human 4-1BB and 4-1BB L Proteins

Analysis of the binding response between R&D Systems Recombinant Human 4-1BB and Recombinant Human 4-1BB Ligand proteins.

Human 4-1BB Ligand Binds 4-1BB. Recombinant Human 4-1BB/TNFRSF9 (R&D Systems, Catalog # 9220-4B) was immobilized at 50 ng/mL and the indicated concentrations of Recombinant Human 4-1BB Ligand (R&D Systems, Catalog # 2295-4L) were added. Recombinant Human 4-1BB Ligand bound with an ED50 of 2.5-15 ng/mL.

Assessment of the Bioactivity of R&D Systems Recombinant Human CD27 Ligand Protein

Analysis of the effect of R&D Systems Recombinant Human CD27 Ligand protein on IL-8 secretion by human fibrosarcoma cells.

CD27 Ligand/CD70 Induces IL-8 Secretion by Human Fibrosarcoma Cells. HT1080 human fibrosarcoma cells transfected with human CD27 were treated with the indicated concentrations of Recombinant Human CD27 Ligand/TNFSF7 (R&D Systems, Catalog # 9328-CL). IL-8 secretion was measured in cell culture supernatants using the Human IL-8/CXCL8 QuantikineTM ELISA Kit (R&D Systems, Catalog # D8000C). The ED50 for this effect is 5-25 ng/mL.

Analysis of the Binding of R&D System Recombinant Human CD40 and CD40 L Proteins

Analysis of the binding response between R&D Systems Recombinant Human CD40 and Recombinant Human CD40 Ligand proteins.

CD40/TNFRSF5 Binds to CD40 Ligand. Recombinant Human CD40 Ligand/TNFSF5 (R&D Systems, Catalog # 6420-CL; HEK293-expressed) was immobilized at 2 μg/mL, 100 μL/well and the indicated concentrations of Avi-tag Biotinylated Recombinant Human CD40/TNFRSF5 Fc Chimera (R&D Systems, Catalog # AVI10380) were added. The concentration of Avi-tag Biotinylated Recombinant Human CD40 that produces 50% optimal binding is 40-320 ng/mL.

Analysis of the Binding of R&D Systems Recombinant Human GITR and GITR L Proteins

Analysis of the binding response between R&D Systems Recombinant Human GITR and Recombinant Human GITR Ligand proteins.

GITR Binds to GITR Ligand. Recombinant Human GITR Ligand/TNFSF18 (R&D Systems, Catalog # 6987-GL) was immobilized at 0.5 μg/mL, 100 μL/well and the indicated concentrations of Avi-tag Biotinylated Recombinant Human GITR/TNFRSF18 Fc Chimera (R&D Systems, Catalog # AVI689) were added. Avi-tag Biotinylated Recombinant Human GITR/TNFRSF18 bound with an ED50 of 0.05-0.5 μg/mL.

Assessment of the Binding Activity and Purity of R&D Systems Recombinant Human OX40 Protein

Analysis of the binding response between R&D Systems Recombinant Human OX40 and Recombinant Human OX40 Ligand proteins.

OX40 Ligand Binds to OX40/TNFRSF4. Recombinant Human OX40/TNFRSF4 (R&D Systems, Catalog # 9969-OX) was immobilized at 0.25 μg/mL and the indicated concentrations of Recombinant Human OX40 Ligand/TNFSF4 (R&D Systems, Catalog # 1054-OX) were added. Recombinant Human OX40 Ligand bound with an ED50 of 0.25-1.5 ng/mL.

Purity of R&D Systems Recombinant Human OX40 protein assessed by SDS-PAGE under reducing and non-reducing conditions.

Assessment of the Purity of Recombinant Human OX40/TNFRSF4 by SDS-PAGE. The purity of Recombinant Human OX40/TNFRSF4 (R&D Systems, Catalog # 9969-OX) was assessed by SDS-PAGE analysis under reducing (R) and nonreducing (NR) conditions and visualized by Coomassie® Blue staining.