Carcinoembryonic antigen-related cell adhesion molecule family (CEACAM family)

The Carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family consists of highly glycosylated cell surface glycoproteins belonging to the immunoglobulin superfamily (1.1.3, 1.2.1). Members such as CEACAM1, CEACAM5 (CEA), and CEACAM6 are frequently overexpressed in various solid tumors, including pancreatic, lung, and colorectal cancers, where they promote tumor progression, metastasis, and immune evasion (1.1.1, 1.3.4). CEACAM1 acts as an inhibitory immune checkpoint on T cells and NK cells by recruiting SHP-1/2 phosphatases via its cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs) (1.1.2, 1.3.2). CEACAM6 contributes to oncogenesis by promoting anoikis resistance, angiogenesis, and chemoresistance through the activation of pathways like PI3K/Akt and MAPK (1.3.1, 1.4.2). Therapeutic strategies include monoclonal antibodies like MK-6018 (CM-24) and tinurilimab, as well as antibody-drug conjugates like tusamitamab ravtansine, which aim to disrupt these pathological interactions or selectively eliminate cancer cells (2.1.1, 2.3.1, 2.4.2). However, the expression of CEACAMs on normal granulocytes and epithelial tissues presents significant safety challenges, including risks of neutropenia and cytokine release syndrome (2.5.1).

Other names

Carcinoembryonic antigen familyCEA familyCD66 familyBiliary glycoprotein (CEACAM1)Non-specific cross-reacting antigen (CEACAM6)CD66a (CEACAM1)CD66c (CEACAM6)CD66e (CEACAM5)

Blockade of homophilic and heterophilic protein-protein interactions to inhibit immune evasion; inhibition of ITIM-mediated inhibitory signaling in T cells and NK cells; induction of anoikis in cancer cells; delivery of cytotoxic payloads via antibody-drug conjugates.