PD-L1 / TIGIT

Class

PD-L1 x TIGIT bispecific antibody

Pathway

dual immune checkpoint blockade (PD-1/PD-L1 and TIGIT/CD155)

PD-L1 and TIGIT are two distinct "checkpoint" molecules that tumors exploit to blunt immune attack. PD-L1, displayed on tumor and stromal cells, engages the PD-1 receptor on T cells, delivering an inhibitory signal that dampens their killing activity. TIGIT is a separate inhibitory receptor found on T cells and natural killer (NK) cells; when it binds its ligand CD155, it similarly restrains immune cell function and additionally interferes with a competing activating receptor, CD226, that would otherwise promote immune engagement. A bispecific antibody targeting both PD-L1 and TIGIT is designed to block two independent inhibitory circuits simultaneously with a single molecule, aiming to restore both T-cell and NK-cell activity against tumor cells more completely than blocking either pathway alone. This dual blockade rationale reflects observations that tumors resistant to PD-1/PD-L1 blockade alone often maintain TIGIT-mediated suppression, and that combining checkpoint inhibition can broaden the immune cell populations engaged, including NK cells, which are not directly reactivated by PD-1/PD-L1 blockade. Such mechanisms are broadly relevant across solid tumors where the tumor microenvironment relies on multiple, overlapping immune-evasion pathways, and represent an extension of the immune checkpoint inhibitor class rather than a single-target approach.