VSTM family: New B7-like immune checkpoint targets?

The B7-like proteins play critical immunomodulatory roles and constitute attractive targets for the development of novel immunotherapies. There are a range of related proteins yet to be studied for their effect on the immune system. R&D Systems researchers have screened several proteins from the VSTM family and find many exhibit immunosuppressive activity.

V-set and transmembrane domain containing (VSTMs) belong to the immunoglobulin (Ig) superfamily of transmembrane proteins. VSTMs have been shown to have 8 members: VSTM1v1, VSTM1v2, VSTM2a, VSTM2b, VSTM2L, TIGIT (VSTM3, VSIG9), VSTM4 and VSTM 5. Most VSTMs are type I transmembrane molecules that contain an extracellular IgV-like domain and one or more cytoplasmic ITIM motifs. The most well-known member is TIGIT (VSTM3), an immune inhibitory receptor that plays a central role in downregulating the T cell-mediated immune response against cancer cells. Our in-house data show that several VSTM family members exhibit similar inhibitory activity on T cell activation.

R&D Systems exclusively offers bioactive recombinant VSTM proteins to further research on these molecules. Use our industry-leading proteins to identify binding partners for orphan B7 and VSTM proteins and discover novel therapies for immune checkpoint blockade.

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VSTM2B inhibits IFN-gamma secretion by PBMCs. Recombinant Human VSTM2B Fc Chimera (Catalog # 10060-VT) inhibits anti-CD3 antibody induced IFN-gamma production in human peripheral blood mononuclear cells. The ED50 for this effect is 1.5-7.5 μg/mL.	VSTM4 inhibits IFN-gamma secretion by PBMCs. Recombinant Human VSTM4 Fc Chimera (Catalog # 2086-VT) inhibits anti-CD3 antibody induced IFN-gamma production in human peripheral blood mononuclear cells. The ED50 for this effect is 1-10 μg/mL.	Recombinant Human TIGIT Fc Chimera binds to Human CD155/PVR. When Recombinant Human CD155/PVR (Catalog # 2530-CD) is immobilized at2.5 µg/mL, Recombinant Human TIGIT Fc Chimera (Catalog # 7898-TGB)binds with an ED50 of 40-200 ng/mL.

Recombinant Human CD155/PVR Fc protein (Catalog # 9174-CD) was immobilized on a Biacore Sensor Chip CM5, and binding to Recombinant Human TIGIT (A103) Fc protein (Catalog # 7898-TGB)  was measured at a concentration range between 0.531 nM and 544 nM. The double-referenced sensorgram was fit to a 1:1 binding model to determine the binding kinetics and affinity, with an affinity constant of KD=67.7 nM.

View other Immune-checkpoint blockade targets

• Butyrophilins
• AMIGOs
• LILRA/B Receptors
• B7/CD28 Family
• CEACAM
• VSIG
• VSTM

Related Pathways

T Cell Co-Signaling Pathway: Ligand-Receptor Interactions

Mechanisms of Regulatory T Cell-Mediated Suppression

Other immune-checkpoint blockade resources:

• Current and Emerging Immune Checkpoint Targets for Immuno-Oncology Research eBook
• Non-Human Primate Recombinant Proteins
• Avi-tag Biotinylated Proteins
• Immune Checkpoint
• Immune Checkpoint Blockade: Immune Checkpoint Molecule Expression
• Immune Checkpoint Blockade: Immune Cell Phenotyping and Isolation
• Immune Checkpoint Blockade: T Cell Responses
• VSIG8 Poster: Co-inhibitory Immune Checkpoint Molecule
• Webinar Short: B7-related Butryophilins as Immune Modulators
• Immunotherapy
• A Role for VSIG-3/VISTA Signaling in Acquired Resistance to Anti-PD-1 Therapy?

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