Definition

A synthetic tumor targeted immune cell agonist composed of two bicyclic peptides targeting CD137 (4-1BB; tumor necrosis factor receptor superfamily member 9; TNFRSF9) linked to a bicyclic peptide targeting the cell adhesion molecule nectin-4 (PVRL4); with potential immunostimulating and antineoplastic activities. Upon administration, CD137/nectin-4 bispecific-targeting agent BT7480 simultaneously targets and binds to CD137, which is expressed on a variety of leukocyte subsets including activated T lymphocytes, and nectin-4 expressed on tumor cells. The simultaneous binding to nectin-4 and CD137 allows for conditional stimulation of CD137 signaling within the tumor microenvironment (TME) only upon binding to nectin-4 on tumor cells. CD137 activation results in T-cell stimulation and enhances T-lymphocyte-mediated anti-tumor immune response against nectin-4-expressing tumor cells. Nectin-4, a tumor associated antigen (TAA) belonging to the nectin family, is overexpressed in a variety of cancers, but has a restricted distribution in normal tissue. CD137, a surface glycoprotein of the tumor necrosis factor receptor superfamily, is an inducible costimulatory receptor that plays a key role in T-cell proliferation, survival and cytolytic activity.