The GPC3 provides an instruction for a protein named glypican 3 and it also called DGSX, GTR2-2, MXR7, OCI-5, SDYS, SGB, SGBS or SGBS1. GPC3 is a cell surface protein that is highly expressed in some human cancers, such as hepatocellular carcinoma, melanoma. The GPC3 encodes a 70-kDa precursor core protein, which can be cleaved by furin to generate an N-terminal protein of 40-kDa amino and a C-terminal protein of 30-kDa membrane-bound carboxyl, that has two heparan sulfate (HS) glycan chains. The GPC3 protein is attached to the cell membrane through a glycosyl-phosphatidylinositol (GPI) anchor. Several studies have shown that GPC3 interacts with other proteins at the surface of cells to restrain cell proliferation. Therefore, it is believed that GPC3 may work as a tumor suppressor and prevent some cell types from growing.
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.