The EPCAM gene provides an instruction for the protein named epithelial cellular adhesion molecule. It is a type I membrane protein of 314 amino acids in humans, which consists of a large extracellular domain (N-terminal) of 242 amino acids, a short cytoplasmic domain of 26 amino acids (C-terminal) and a single-spanning transmembrane domain of 23 amino acids. The encoded EPCAM gene is located on the chromosome 2p21 and estimated with a size of 14 kb. This transmembrane glycoprotein with approximately 35kDa mediates Ca2+-independent homotypic cell-cell adhesion in epithelial cells and responses to cell surface interactions at the vascular wall. Diseases linked to EPCAM include congenital and colorectal cancer, with tufting enteropathy, and so on. It is used as a target for immunotherapy treatments of human cancer.
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.