The CD8 molecule is not only the immune system’s identification badge, but also a rising star in cancer immunotherapy. According to the latest report in Nature Reviews Drug Discovery, 17 CD8-targeting drugs have already entered clinical stages worldwide. Today, we dive through the cell membrane to see how this 34 kDa glycoprotein became a key player on the anticancer battlefield.
CD8 is a transmembrane glycoprotein predominantly expressed on the surface of CD8+ T cells and serves as an essential co-receptor for the T cell receptor (TCR). Its core functions include: assisting antigen recognition by enhancing TCR engagement with antigen-presenting cells (APCs) or target cells; mediating signal transduction, where CD8 facilitates TCR signaling by recruiting tyrosine kinase p56lck; and regulating immune homeostasis. In the gut, CD8αα on intraepithelial lymphocytes (IELs) binds thymus leukemia antigen (TL) on intestinal epithelial cells (IECs), suppressing IEL proliferation to prevent excessive inflammation. CD8+ T cells are key effector cells in antitumor immunity, but in gastric cancer (GC) and colorectal cancer (CRC), they often become exhausted, leading to tumor immune escape.
Through structural diversity (αβ or αα dimers) and broad expression in T cells, thymocytes, NK cells, and other immune cells, CD8 plays a central role in antigen recognition, signal transduction, and immune homeostasis. Its multifunctionality makes it an indispensable co-receptor in the immune system. Common CD8 structures include heterodimers (CD8αβ) and homodimers (CD8αα), and like most membrane proteins, it contains extracellular domains and a transmembrane region. The molecular weights of the α and β chains are similar: approximately 34–37 kDa (α chain) and 32 kDa (β chain).
As a core regulatory molecule in T cell immune responses, CD8 has become an important therapeutic target for cancer, autoimmune disease, and infectious disease. Globally, CD8-targeting drugs span bispecific antibodies, cell therapies, radiopharmaceuticals, and small-molecule inhibitors. Below is an overview of CD8-targeted agents currently in clinical development:
To support CD8-related drug development and clinical research, Kyinno Biotechnology has developed CD8-related engineered cell lines of multiple species using its advanced engineered-cell technology platform. These include engineered cell lines overexpressing human, cynomolgus monkey, or mouse CD8a, CD8b, or co-expressed CD8a/CD8b in mouse colorectal cancer cell lines MC38/CT26, Chinese hamster ovary epithelial cells CHO-K1, and human embryonic kidney 293T cells. In addition, Kyinno Biotechnology provides services including control antibody/protein expression, antibody discovery, antibody off-target validation, and in vivo/in vitro pharmacology studies. Contact us for more information.
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