anti-claudin18.2/anti-CD3 bispecific antibody AZD5863

An affinity-optimized T-cell engaging (TCE) and human bispecific antibody directed against the tumor-associated antigen (TAA) Claudin18.2 (CLDN18.2; A2 isoform of claudin-18) and the human T-cell surface antigen CD3, with potential immunostimulatory and antineoplastic activities. Upon administration, anti-CLDN18.2/anti-CD3 bispecific antibody AZD5863 simultaneously targets and binds to both CLDN18.2-expressing tumor cells, with bivalent high affinity binding, and CD3-expressing T cells, with monovalent low affinity binding. This crosslinks CLDN18.2-expressing tumor cells and cytotoxic T lymphocytes (CTLs) and results in the activation and proliferation of T cells. This causes a CTL-mediated cell lysis of CLDN18.2-expressing tumor cells. Additionally, AZD5863 induces bystander killing of CLDN18.2-negative tumor cells. 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. The bivalent high-affinity binding to CLDN18.2 and monovalent low-affinity binding to CD3 of AZD5863 may reduce toxicities while optimizing specific anti-tumor activity.