Definition

A bispecific antibody composed of a human, Fc-silenced immunoglobulin G1 (IgG1) monoclonal antibody targeting the tumor-associated antigen (TAA) Claudin18.2 (CLDN18.2; A2 isoform of claudin-18) fused with a single chain variable fragment (scFv) targeting 4-1BB (CD137; tumor necrosis factor receptor superfamily member 9; TNFRSF9), with potential immunostimulating and antineoplastic activities. Upon administration, anti-CLDN18.2/anti-4-1BB bispecific antibody TJ-CD4B simultaneously targets and binds to CLDN18.2 expressed on tumor cells and 4-1BB expressed on a variety of leukocyte subsets including activated T lymphocytes. Upon CLDN18.2 binding, the 4-1BB activation signal is induced and TJ-CD4B acts as a conditional 4-1BB agonist in the tumor microenvironment (TME), resulting in T-cell co-stimulation and T-lymphocyte-mediated anti-tumor activity. CLDN18.2, a tight junction protein and stomach-specific isoform of claudin-18, is expressed on a variety of tumor cells. Its expression in healthy tissues is strictly confined to short-lived differentiated epithelial cells of the gastric mucosa. 4-1BB, 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.