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1. Novel strategy for anti-PD-1/PD-L1 treatment resistance
Banta, Karl L et al. “Mechanistic convergence of the TIGIT and PD-1 inhibitory pathways necessitates co-blockade to optimize anti-tumor CD8+ T cell responses.” Immunity vol. 55,3 (2022): 512-526.
(1) Despite the great clinical success of immune checkpoint inhibitors, approximately 70% of patients still exhibit ineffective and adaptive resistance in PD-1/PD-L1 blockade anti-tumor therapy.
(2) TIGIT is an inhibitory receptor, mainly expressed on NK cells and activated T cells and Treg cells. Dual blockade retains the pharmacodynamic activity of PD-1 inhibitors and inhibits the signal of TIGIT simultaneously, which synergistically enhances the efficacy. PD-1×TIGIT BsAb can be a strategy to overcome PD-1/PD-L1 blockade anti-tumor therapy resistance.
2. Asset binds to PD-1 and TIGIT simultaneously.
The asset is able to block both PD-1/PD-L1 pathway and TIGIT/CD155 pathway in vitro.
3. Excellent anti-tumor efficacy.
(1) The asset shows enhanced SEB-induced-INF-γ secretion compared with Keytruda (anti-PD-1 mAb) and Tiragolumab (anti-TIGIT mAb) combination therapy, which remains more T cell activation.
(2) The asset showed superior antitumor activity compared to the combination of Keytruda and Tiragolumab in vivo.
4. Good safety in preclinical study.
Cynomolgus monkeys were administered 3 weekly doses of 25 or 50 mg/kg of asset.
✓ All animals were survived.
✓ No toxicologically significant abnormalities were observed.
✓ NOAEL dose: 50 mg/kg.
1. Asset type: PD-1×TIGIT BsAb
2. Indication: Advanced solid tumor
4. Research phase: Preclinical
5. Cooperation demands: License-out or co-development
6. Research progress:
1. Preclinical stage
2. Anti-tumor efficacy in preclinical study
3. Good safety
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