Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) N-terminal IgV-like domain (CEACAM5 N-domain)

The N-terminal IgV-like domain of Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), also known as CEA or CD66e, is the most distal extracellular region of this GPI-anchored glycoprotein (NIH, 2011). This domain is a member of the immunoglobulin superfamily and is critical for mediating both homophilic and heterophilic cell-cell adhesion (PNAS, 2015). In healthy tissues, CEACAM5 is expressed on the apical surface of epithelial cells, but in various cancers—such as colorectal, non-small cell lung, and gastric carcinomas—it is overexpressed and loses its polarized distribution (MDPI, 2024). The N-terminal domain specifically facilitates tumor progression by inhibiting anoikis and promoting metastatic implantation through interactions with the extracellular matrix and other cells (NIH, 2021). Additionally, this domain serves as a docking site for various bacterial pathogens, including Helicobacter pylori and Escherichia coli (NIH, 2026). Because of its high tumor-to-normal expression ratio and its role in oncogenic signaling, the CEACAM5 N-terminal domain is a key target for novel immunotherapies, including bispecific antibodies like NILK-2401 and antibody-drug conjugates (ADCs) (NIH, 2024).

Other names

CEA N-terminal domainCD66e N-terminal domainCarcinoembryonic antigen N-terminal domainCEACAM5 IgV domainCEACAM5 N-domain

Antibody-drug conjugates (ADCs) target the extracellular domains of CEACAM5 to deliver cytotoxic payloads, while bispecific antibodies recruit T-cells or block immune checkpoints on CEACAM5-expressing tumor cells (NIH, 2021; DelveInsight, 2024). Specific targeting of the N-terminal domain can also block homophilic and heterophilic cell adhesion, inhibiting tumor metastasis and pathogen entry (PNAS, 2015; NIH, 2026).