PD-1 and LAG-3

Class

PD-1/LAG-3 bispecific antibody (tobemstomig)

Pathway

T-cell checkpoint immune inhibition

PD-1 and LAG-3 are both inhibitory receptors expressed on the surface of T cells, the immune cells responsible for recognizing and killing abnormal or infected cells. Under normal conditions, these receptors act as brakes that prevent excessive or prolonged immune activation. Tumors exploit this biology by displaying ligands that engage PD-1 and LAG-3, driving T cells into a dysfunctional state called exhaustion, in which they lose the ability to attack cancer cells. Blocking PD-1 alone can restore some T-cell activity, but many tumors that resist this approach show increased LAG-3 expression as a compensatory escape route. A bispecific antibody that engages both PD-1 and LAG-3 simultaneously targets two distinct but overlapping inhibitory pathways on the same exhausted T-cell population, aiming to produce a more complete reactivation than blocking either receptor alone. This dual-checkpoint strategy is relevant across cancers where T cells infiltrate tumors but remain functionally suppressed, including settings where single-agent checkpoint blockade has shown limited or waning benefit. The approach reflects a broader principle in immuno-oncology: multiple, partially redundant inhibitory signals often need to be addressed together to unlock a durable anti-tumor immune response.