EGFR x 4-1BB (CD137)

Class

EGFR/4-1BB bispecific antibody (tumor-targeted immune costimulator)

Pathway

EGFR signaling blockade combined with 4-1BB-mediated T-cell/NK-cell costimulation

EGFR (epidermal growth factor receptor) is a cell-surface receptor tyrosine kinase that is frequently overexpressed or mutated in epithelial cancers such as lung, colorectal, and head-and-neck tumors, where it drives proliferation and survival signaling. 4-1BB (also called CD137) is a costimulatory receptor found on activated T cells and natural killer (NK) cells; when engaged, it strengthens their persistence, proliferation, and tumor-killing capacity. This bispecific antibody links the two functions: one arm binds EGFR on tumor cells, and the other engages 4-1BB on nearby immune cells. Because 4-1BB is only clustered and activated where EGFR is present, immune costimulation is concentrated within the tumor rather than occurring broadly throughout the body, a limitation that has hampered stand-alone 4-1BB agonists, which can cause diffuse immune activation and liver inflammation when unconstrained. Pairing EGFR targeting with 4-1BB engagement is intended to combine direct interference with tumor growth signaling with a localized boost to anti-tumor immunity, an approach relevant across EGFR-driven or EGFR-expressing solid tumors where enhancing T-cell and NK-cell activity within the tumor microenvironment could improve outcomes beyond either mechanism alone.