EGFR and CD28

Class

EGFR x CD28 costimulatory bispecific antibody (marlotamig)

Pathway

T-cell costimulation coupled to EGFR-expressing tumor cell engagement

This mechanism involves a bispecific antibody engineered to bind two distinct targets simultaneously: the epidermal growth factor receptor (EGFR), a protein frequently overexpressed on the surface of epithelial tumor cells, and CD28, a costimulatory receptor found on T cells, the immune system's primary tumor-killing lymphocytes. Full T-cell activation typically requires two coordinated signals: recognition of an antigen (signal one) and a costimulatory signal (signal two, normally delivered through CD28 binding its ligands on antigen-presenting cells). Tumors often evade immune attack partly by lacking these costimulatory ligands, leaving T cells under-activated even when they recognize tumor antigens. By physically bridging CD28 on T cells to EGFR on tumor cells, this bispecific antibody delivers costimulation directly at the tumor site, intended to amplify T-cell activity specifically where the cancer resides rather than throughout the body. This approach is generally understood to work alongside separate T-cell-engaging therapies that supply the primary activation signal, with the costimulatory bispecific reinforcing and sustaining that response. The broad disease relevance spans EGFR-expressing solid tumors, where boosting local T-cell function without triggering widespread immune activation is a central therapeutic goal.