Protease-activated Anti-EGFR/Anti-CD3 Bispecific Antibody Prodrug CX-904

**Semantic type:** Amino Acid, Peptide, or Protein|Immunologic Factor|Pharmacologic Substance

**Definition:** A recombinant bispecific antibody prodrug composed of a bispecific antibody directed against the tumor-associated antigen (TAA) human epidermal growth factor receptor (EGFR; HER1; ErbB1) and the human T-cell surface antigen CD3 that is linked to a proprietary masking peptide through a protease-cleavable linker, with potential immunostimulating and antineoplastic activities. Upon administration of protease-activated anti-EGFR/anti-CD3 bispecific antibody prodrug CX-904, the linkage system is stable in the circulation and, upon extravasation into the tumor microenvironment (TME), the peptide mask is cleaved by tumor-associated proteases. These proteases are present in high concentrations and aberrantly activated in the TME, while expressed as inactive forms, at much lower concentrations, in normal, healthy tissue. Protease cleavage of the linker enables binding of the unmasked, fully active bispecific antibody moiety of CX-904 to both CD3 on cytotoxic T-lymphocytes (CTLs) and EGFR on EGFR-expressing tumor cells. This activates and redirects CTLs to EGFR-expressing tumor cells, leading to CTL-mediated killing of EGFR-expressing tumor cells. EGFR, upregulated and/or mutated in a variety of tumor cell types, plays a key role in tumor cell proliferation and survival.

**Synonyms:** - AMG 651 - AMG-651 - AMG651 - Anti-EGFR/Anti-CD3 Bispecific Probody AMG 651 - Anti-EGFR/Anti-CD3 Bispecific Probody CX-904 - Anti-EGFR/Anti-CD3 T-cell Engaging Bispecific Probody AMG 651 - Anti-EGFR/Anti-CD3 T-cell Engaging Bispecific Probody CX-904 - Anti-EGFR/CD3 Bispecific Antibody Prodrug CX-904 - CX 904 - CX-904 - CX904 - EGFR x CD3 Bispecific Antibody Prodrug CX-904 - T-cell-engaging Bispecific Antibody CX-904 - TCB Antibody CX-904