Definition

A dual-targeting bispecific antibody and T-cell engager (BiTE) co-targeting both the human tumor-associated antigens (TAAs) cadherin-3 (CDH3; placental cadherin; P-cadherin) and mesothelin (MSLN) on tumor cells and CD3 antigen found on T lymphocytes, with potential immunostimulating and antineoplastic activities. Upon administration, anti-CDH3/MSLN BiTE antibody AMG 305 binds with specificity to tumor cells co-expressing CDH3 and MSLN antigens and CD3 on cytotoxic T-lymphocytes (CTLs). This results in the cross-linking of T cells and tumor cells, and induces a cytotoxic T-lymphocyte (CTL) response against CDH3- and MSLN-co-expressing tumor cells. CDH3 is a member of the cadherin family; it is overexpressed in a variety of tumors and plays a role in cell adhesion, motility, invasion, and proliferation. Mesothelin, a cell surface glycoprotein involved in cell adhesion, is overexpressed in a variety of cancer cell types. Binding of both CDH3 and MSLN allows for increased specificity in targeting these TAAs that may be expressed at low levels on the tumor surface while limiting activity against normal cells that express only one of the target antigens.