Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) (CEACAM5)

Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), commonly known as Carcinoembryonic Antigen (CEA), is a cell surface glycoprotein that belongs to the immunoglobulin superfamily [UniProt: P06731]. It is primarily expressed during fetal development and is found at low levels in normal adult intestinal, pancreatic, and hepatic tissues [StatPearls: NBK554413]. However, it is significantly overexpressed in various solid tumors, most notably in over 90% of colorectal carcinomas, where it plays a critical role in promoting tumor cell adhesion, migration, and resistance to anoikis [PubMed: 32800310]. Because of its high tumor specificity and accessibility on the cell surface, CEACAM5 serves as both a gold-standard diagnostic biomarker for monitoring cancer recurrence and a compelling therapeutic target [NCI Thesaurus: C300]. Current pharmacological strategies targeting CEACAM5 include antibody-drug conjugates (ADCs) like tusamitamab ravtansine, bispecific T-cell engagers such as cibisatamab, and CAR-T cell therapies [PubMed: 34154942, PubMed: 31061205]. These treatments aim to leverage the differential expression between malignant and normal tissues to deliver cytotoxic agents or recruit the immune system directly to the tumor site. While therapeutic development is promising, challenges include potential on-target off-tumor toxicity in healthy epithelial tissues and the heterogenous expression of the antigen within large tumors [PubMed: 25164213].

Other names

CEACarcinoembryonic antigenCD66eMeconium antigen 100Colorectal carcinoma-associated antigenCarcinoembryonic antigen-related cell adhesion molecule 5

Targeting involves antibody-drug conjugation (ADC) for the delivery of cytotoxic agents (e.g., maytansinoids or topoisomerase inhibitors), bispecific T-cell redirection (CEA-TCB), and immune-cytokine stimulation to induce tumor cell lysis (PubMed: 32800310, PubMed: 34154942).