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Your Position: Home > News > TIGIT: an emerging immue checkpoint target
TIGIT: an emerging immue checkpoint target
Release time: 2020-07-07 Source: ACRO Read: 567

The 2020 American Society of Clinical Oncology (ASCO) just ended a month ago. Due to the impact of the COVID-19 pandemic, they successfully moved the meeting to virtual. The ASCO Annual Meeting, which is one of the largest clinical oncology conferences worldwide, serves as a platform for oncology professionals to share the latest progress in the clinical oncology field. This year, updates around TIGIT, BCMA, CD47 as well as some other targets were shared.


Roche announced their positive Phase II clinical trial data of the tiragolumab, an anti-TIGIT monoclonal antibody, which drew a lot of attention. Their result shows a 67% reduction in the risk of disease worsening or death (median PFS=not reached vs 3.9 months; HR=0.33, 95% CI: 0.15–0.72) with the combination compared with Tecentriq alone. This positive result brings out a new idea that blockade of TIGIT and PD-L1 may synergistically enable the re-activation of T-cells and enhance NK cell anti-tumor activity.


TIGIT was initially discovered in a genomic search for genes specifically expressed in T cells that had protein domain structures representative of potential inhibitory receptors. TIGIT fulfills the role of coinhibitory receptors to counterbalance the costimulatory function of CD226. TIGIT competes with immunoactivator receptor CD226 (DNAM-1) for the same set of ligands: CD155 (PVR or poliovirus receptor) and CD112 (Nectin-2 or PVRL2). The expression of TIGIT has been demonstrated in both NK cells and T cells and plays a role in their activation and maturation.

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Figure 1. A: Expression and Interactions of PVR Family Members; B: Inhibition of the Cancer Immunity Cycle by TIGIT.


Emerging studies have shown that blockade of TIGIT might be a potential supplement for existing immunotherapies. TIGIT has demonstrated great promise in preclinical models as a new target for cancer immunotherapy and potentially may work synergistically to expand the activity of approved checkpoint inhibitors, like anti-PD-1, anti-CTLA-4, etc. There are around 20 clinical trial studies around TIGIT going on according to the record of FDA.


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Table 1. Selected TIGIT Targeted Research Summary 

 

Roche's anti-TIGIT antibody tiragolumab has entered Phase III clinical. Other than Roche, there are some other companies following. Innovent Bio’s TIGIT antibody IBI939 is the first to get their NDA approved from CFDA. IBI939 can directly combine with TIGIT to relieve the T cells and NK cells exhaustion, thereby promoting the anti-tumor effect. Meanwhile, it is expected to synergistically enhance the anti-tumor activity of PD-1/PD-L1 antibody drugs. BeiGene has initiated a Phase 1a/1b clinical trial of BGB-A1217 combined with tislelizumab for advanced solid tumors in China and Australia. As more and more pharmaceutical companies joining this competition, TIGIT targeted antibody development will become a future trend.


ACROBiosystem has developed a series of TIGIT recombinant proteins to facilitate the development of antibodies and the screening of inhibitors. The products are verified as a homodimer by MALS and are suitable for various applications during the drug development process.


Assay Data

➵ Homodimer verified by MALS:

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Fig.1 The purity of Human TIGIT Protein, His Tag (Cat. No. TIT-H52H3) was more than 90% and around 30-45 kDa verified by SEC-MALS.


➵ Application in different phases of drug development:

1593505661326618.png    

Fig.2 Immobilized Human TIGIT, His Tag (Cat. No. TIT-H52H3) at 2 μg/mL (100 μL/well) can bind Human CD155, Fc Tag (Cat. No. CD5-H5251) with a linear range of 8-128 ng/mL.


➵ TIGIT: CD155 inhibitor screening

 1593505661326618.png    

Fig.3 Serial dilutions of Human TIGIT Neutralizing antibody were added into Human CD155, Fc Tag (Cat. No. CD5-H5251): Biotinylated Human TIGIT, Fc,Avitag (Cat. No. TIT-H82F1) binding reactions. The half maximal inhibitory concentration (IC50) is 0.06065 μg/mL.


➵ BLI:

 1594122886380786.jpg

Fig.4 Loaded Human TIGIT, Fc Tag (Cat. No. TIT-H5254) on Protein A Biosensor, can bind Human CD155, His Tag (Cat. No. CD5-H5223) with an affinity constant of 0.98 μM as determined in BLI assay (ForteBio Octet Red96e).


➵ SPR:

 1594123059195911.png 

Fig.5 Anti-Human TIGIT MAb (Mouse IgG1) captured on CM5 chip via Anti-Mouse antibodies surface, can bind Human TIGIT, His Tag (Cat. No. TIT-H52H3) with an affinity constant of 3.93 nM as determined in a SPR assay (Biacore T200).

 

➵ FACS:

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Fig.6 FACS assay shows that Human TIGIT, His Tag (Cat. No. TIT-H52H3) can bind to 293T cell overexpressing human CD155. The concentration of TIGIT used is 0.3 μg/mL.


Product List


Cat. No.SpeciesProduct DescriptionStructurePurityFeature
TAT-K004HumanAnti TIGIT ELISA Kit


TIT-C52H7CanineCanine TIGIT Protein, His Tag
TIT-C52H7-structure
TIT-H5253HumanHuman TIGIT Protein, Mouse IgG2a Fc Tag, low endotoxin
TIT-H5253-structure
TIT-R5259RabbitRabbit TIGIT Protein, Fc Tag
TIT-R5259-structure
TIT-R5258RatRat TIGIT Protein, Fc Tag
TIT-R5258-structure
TIT-C5254Cynomolgus / Rhesus macaqueCynomolgus / Rhesus macaque TIGIT Protein, Fc Tag
TIT-C5254-structure
TIT-H82E5HumanBiotinylated Human TIGIT Protein, Avitag™,His Tag (recommended for biopanning)
TIT-H82E5-structure
TIT-C5223Cynomolgus / Rhesus macaqueCynomolgus / Rhesus macaque TIGIT Protein, His Tag (HPLC-verified)
TIT-C5223-structure
TIT-H82F1HumanBiotinylated Human TIGIT Protein, Fc,Avitag™
TIT-H82F1-structure
TIT-M52E6MouseMouse TIGIT Protein, His Tag
TIT-M52E6-structure
TIT-M5257MouseMouse TIGIT Protein, Fc Tag
TIT-M5257-structure
TIT-H52H3HumanHuman TIGIT Protein, His Tag
TIT-H52H3-structure
TIT-H5254HumanHuman TIGIT Protein, Fc Tag
TIT-H5254-structure


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