We previously addressed the PD-1:PD-L1/PD-L2 immune inhibition and the corresponding cell-based tools to screen immuno-oncology agents for restoring antitumor immune response. Unfortunately cancer cells have other ways to escape and survive. Let look together at another immune inhibition pathway, namely the TIGIT:CD155/CD112.
TIGIT:CD155/CD112 binding stops the natural killers
Human T cells and Natural Killer (NK) cells express an immunoreceptor on their surface called TIGIT, for T-cell immunoreceptor with Ig and ITIM domains. TIGIT binds proteins on the surface of dendritic cells, the CD155 and CD112. This cellular interaction stops the T cell and NK cell activation. Thus, inhibition of this binding increases immune response. Research on this inhibition is a way to develop an immune-based strategy against cancers.
Research and development to restore immune response
Antibodies such as the neutralizing antibody anti-TIGIT (by BPS) and other agents can specifically block this cell surface protein binding and activate the immune response as illustrated above and shown in the cell-based assays results below.
In order to test and optimize new agents, a robust TIGIT:CD155 homogeous assay will provide answer within a day.
Furthermore, BPS is now introducing an innovation allowing a cell-based assay closer to the in vivo situation. The teams at BPS have established and validated (thanks notably to the neutralizing anti-TIGIT) 2 complementary reporter cell lines:
- The TIGIT /NFAT Reporter cell line (60538) is an Jurkat cell line so the T-cell in the interaction model
- The CD155/TCR Activator Cell line (60548) that corresponds to recombinant CHO-K1 cells constitutively expressing human CD155 and an engineered T cell receptor (TCR) activator.
Combining them together, we get a new assay in cellular context. From now on, researchers can investigate antagonistic monoclonal antibodies targeting either TIGIT or its ligand CD155.
Positive controls, the 2 anti-TIGIT antibodies
The anti-TIGIT (71218), called inhibitor antibody can be used to block the TIGIT:CD115/CD112 binding in vitro. It is the recommended positive control for biochemical assays.
For cell-based assays, the positve control is the anti-TIGIT (71340), called neutralizing antibody. It can be use with the luciferase reporter TIGIT /NFAT cell line (60538) and the CD155/TCR Activator Cell line (60548).
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