Surface-exposed tissue proteins

Surface-exposed tissue proteins, collectively known as the surfaceome, comprise the set of proteins located on the external surface of cells within various tissues. These proteins serve as the primary interface between the cell and its environment, facilitating critical processes such as signal transduction, nutrient transport, and cell-cell adhesion (The Scientist, 2021). Because they are directly accessible to molecules in the extracellular space, they are the most common targets for therapeutic antibodies, antibody-drug conjugates (ADCs), and other large-molecule biologics (ACS, 2018). In oncology, many surface-exposed proteins like HER2 and EGFR are overexpressed, allowing for targeted destruction of tumor cells while sparing healthy tissue (MDPI, 2021). In infectious diseases, surface proteins of pathogens are targeted by vaccines to elicit protective immune responses (NIH, 2022). However, the therapeutic use of these targets is often limited by on-target, off-tumor toxicity, where the target is also expressed on vital healthy organs, leading to adverse effects.

Other names

Cell surface proteinsSurfaceomeMembrane-associated proteinsExtracellularly exposed proteinsCell surface antigens

Binding to extracellular domains to modulate signaling, induce immune-mediated cell killing (ADCC/CDC), or deliver conjugated cytotoxic payloads.