PD-L1 + 4-1BB (CD137)

Class

PD-L1/4-1BB bispecific antibody (opamtistomig)

Pathway

PD-L1 checkpoint blockade combined with 4-1BB costimulatory agonism to enhance anti-tumor T-cell activity

PD-L1 is a protein expressed on tumor cells and some immune cells that normally engages the receptor PD-1 on T cells, delivering an inhibitory signal that dampens T-cell attack on tissue, including tumors that hijack this checkpoint to evade immune destruction. 4-1BB (CD137) is a costimulatory receptor found on activated T cells and other immune cells; when engaged, it reinforces T-cell survival, proliferation, and cytotoxic function. A bispecific antibody that targets both aims to combine two complementary actions: blocking the inhibitory PD-L1/PD-1 checkpoint while simultaneously delivering a costimulatory boost through 4-1BB. Because 4-1BB agonists given alone can activate immune cells throughout the body, pairing 4-1BB engagement with a PD-L1-binding arm is intended to concentrate that activation at sites where PD-L1 is abundant, typically the tumor and its surrounding tissue. This dual mechanism is broadly relevant to solid tumor types in which checkpoint blockade alone produces limited or short-lived responses, with the rationale that adding localized costimulation may generate a more durable and potent anti-tumor T-cell response than blocking the checkpoint alone.