CD63, also known as Tetraspanin-30 (Tspan-30), lysosomal-associated membrane protein 3 (LAMP-3), lysosome integral membrane protein 1 (Limp1), melanoma-associated antigen (ME491), and ocular melanoma-associated antigen (OMA81H), is a multi-transmembrane protein that plays a role in cancer malignancy.¹

CD63 is a highly N-glycosylated member of the transmembrane-4 superfamily of tetraspanin proteins. CD63 is composed of 238 amino acids comprising four transmembrane α-helices, two extracellular loops, and a short cytoplasmic tail. CD63 is located in late endosomes, lysosomes, secretory vesicles, and the plasma membrane. At the plasma membrane, CD63 interacts with cell adhesion molecules such as integrins in order to regulate intracellular signaling pathways for cell adhesion, motility, and survival. CD63 is also involved in membrane transport, fusion, and protein kinase signaling.^1,2

In addition to its role as a confirmed marker for cancer, the significance of CD63 in identifying exosomes has recently been highlighted. Exosomes are small extracellular vesicles, ranging from 50 to 150 nm in diameter, characterized by a lipid membrane structure. They are widely present in bodily fluids and can be generated by almost all cell types, whether in pathological or physiological conditions. Importantly, the contents of exosomes are carefully regulated by their originating cells, allowing them to convey specific information from the parent cells to other cells. This enables the assessment of the functional states of specific cells by examining the exosomes they release, paving the way for non-invasive cancer liquid biopsies facilitated by exosomes.¹

The presence of specific protein markers on exosomes has been observed, opening up possibilities for the development of an immunoaffinity-based strategy to separate exosomes. This strategy involves exploring the specific binding between these markers and their corresponding affinity agents, such as antibodies. The landscape of present-day biological research is undergoing a significant transformation due to the advancements in exosome-mediated therapeutics and diagnosis. Consequently, CD63 emerges as a highly promising target, not only for evaluating cancer, but also for delivering drugs with precision to tumor cells that express CD63. This targeted approach holds great potential for precise anti-cancer therapy.¹