CEA (Carcinoembryonic antigen) is a type of glycoprotein attached to the cell membrane via glycosylphosphatidylinositol (GPI) anchor and stands for a set of highly related substance implicated in cell adhesion. It belongs to the immunoglobulin superfamily (IgSF) and there are two immunoglobulin domains including an N-terminal domain of 108 amino acids homologous to IgV-like and six domains homologous to the IgC2-like. The CAE gene family in humans is clustered on chromosome 19q and comprises 29 genes, 18 of which are commonly found. CEA is generally expressed in gastrointestinal tissue during embryonic development, but produced in very small amounts after birth. The serum level of it is not raised unless certain cancers tested. The CEA has become one of the most widely used tumor markers in clinical diagnosis and its main application is in gastrointestinal cancers, particularly in colorectal malignancy.
4-1BB (also known as CD137 or TNFRSF9) is a type I transmembrane glycoprotein belonging to the tumor necrosis factor receptor superfamily (TNFRSF). It consists of 255 amino acids with a molecular weight of ~28 kDa, featuring an extracellular domain containing four cysteine-rich motifs, a transmembrane helix, and an intracellular domain critical for downstream signaling. Primarily expressed on activated T cells and natural killer (NK) cells, 4-1BB is upregulated upon T-cell receptor engagement and interacts with its ligand 4-1BBL, which is predominantly displayed on antigen-presenting cells (APCs) like dendritic cells and macrophages. This receptor-ligand interaction recruits TRAF adaptor proteins (TRAF1, TRAF2, TRAF3) to form signalosomes, activating NF-κB and MAPK pathways that enhance T-cell proliferation, cytotoxic activity, and pro-inflammatory cytokine production, while suppressing apoptosis through upregulated anti-apoptotic proteins like Bcl-2. As a pivotal co-stimulatory molecule in adaptive immunity, 4-1BB has emerged as a promising target for cancer immunotherapy.