Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) and Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) interaction (CEACAM5/CEACAM1)

Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), also known as CEA, is a cell surface glycoprotein and member of the immunoglobulin superfamily that is frequently overexpressed in various carcinomas, including colorectal, lung, and breast cancers (UniProt P06731). In the tumor microenvironment, CEACAM5 on tumor cells interacts with CEACAM1 (UniProt P13688), an inhibitory receptor expressed on natural killer (NK) cells and other immune cells (PMID: 16317114). This interaction, often occurring through heterophilic binding, leads to the inhibition of NK cell-mediated cytotoxicity, thereby promoting tumor immune evasion (PMID: 25231358). Targeting this axis is a significant area of research in immuno-oncology, with strategies focusing on blocking the CEACAM5-CEACAM1 interaction to restore immune surveillance. Therapeutic agents under development include monoclonal antibodies, bispecific antibodies, and antibody-drug conjugates (ADCs) such as tusamitamab ravtansine, which targets CEACAM5 to deliver cytotoxic payloads to tumor cells (NCT04154956). Additionally, CEACAM1-specific inhibitors like nelastotug are being investigated for their ability to prevent the inhibitory signaling triggered by CEACAM5 binding. The clinical utility of targeting this interaction is further supported by the use of serum CEA levels as a biomarker for disease progression and treatment response in several cancer types. Safety considerations for these therapies include potential on-target off-tumor effects due to low-level CEACAM5 expression in normal epithelial tissues and specific toxicities associated with ADC payloads.

Other names

CEACD66eCarcinoembryonic antigenBiliary glycoproteinBGPCD66aCEACAM1-CEACAM5 axis

Blocking the heterophilic interaction between CEACAM5 on tumor cells and CEACAM1 on NK cells to prevent inhibitory signaling and restore NK cell-mediated anti-tumor cytotoxicity (PMID: 25231358; PMID: 16317114).