Definition

A tetravalent bispecific antibody targeting both the pro-apoptotic death receptor tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) receptor 2 (TRAILR2; death receptor 5; DR5) and cadherin-17 (CDH17), with potential pro-apoptotic and antineoplastic activities. Upon administration of anti-TRAILR2/CDH17 tetravalent bispecific antibody BI 905711, the antibody targets and binds to both TRAILR2 and CDH17, expressed on tumor cells. Receptor clustering and activation of TRAILR2 induces apoptosis in CDH17-positive cancer cells. Activation of TRAILR2 plays a key role in the induction of apoptosis. CDH17-dependent clustering of TRAILR2 allows BI 905711 to selectively induce apoptosis in CDH17-expressing tumor cells thereby increasing efficacy and decreasing liver toxicity. CDH17 is overexpressed in a variety of cancer cell types while its expression is restricted in normal liver tissue.