CTLA-4 Immune Checkpoint Molecule for Drug Development
introduction to CTLA-4
Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), also known as CD152, ALPS5, CELIAC3, GRD4, GSE, or IDDM12, is a type of CD28 homolog molecule that plays an important role in regulating T cell activation. CTLA-4 is normally present in the vesicles of cells and is then transported to the immune synapse formed between T cells and antigen-presentation cells (APCs) and inhibits further activation of T cells by blocking T cell receptors and their signaling pathways. Pilot studies have demonstrated that the binding of CTLA-4 to its ligands, such as CD80 (B7-1) and CD86 (B7-2), can induce T cells, and the blocking of CLTA-4 molecules can significantly improve T cell activation. Furthermore, CTLA-4 has been regarded as a clinically targeted immune checkpoint molecule and is broadly used in treating various disease types, especially for tumors. For example, CTLA-4 can promote tumor cell survival and tumor immune evasion by downregulating CD80/CD86 expression on certain tumor models.
Fig.1 CTLA-4 structure.
Immune Checkpoint CTLA-4 for Drug Development
In recent years, immune checkpoint molecules, like CTLA-4, have become a powerful tool for preventing immune damage. The immune response of T cells controlled by checkpoint molecules can avoid unwanted activation in disease treatments. Up to now, CTLA-4 molecules have shown an indispensable role in regulating self-tolerance of autoimmune diseases, the T-cell response of infectious diseases, as well as anti-tumor activity of various cancers. The data derived from different disease models have suggested that the blockade of CTLA-4 and CD80/CD86 pathway is effective in antigen-specific tumor elimination in vivo.
Nowadays, various CTLA-4 immune checkpoint inhibitors have been evaluated and approved for treating patients with certain cancers. These inhibitors show anti-tumor activities by blocking CTLA-4 molecules on T cells or their ligands on APCs or tumor cells. Moreover, the safety profiles and efficacies of these CTLA-4 immune checkpoint drugs have been tested in many cancers. Besides, recent advances in tumor immunity have revealed that the blocking of immunosuppressive cells and specific cytokines in a tumor microenvironment (TME) could be a new strategy for the combination of CTLA-4 and other blockers in disease therapy.
As a consequence, with the commitment of being the best immune checkpoint study service provider, Creative Biolabs has established the utmost efficient CTLA-4-based drug development for our worldwide customers, including but not limited to: