Anti-B7-CD28 Family Agonistic Antibody Introduction

With the increasing role played by agonist antibody-targeted co-stimulated receptors, represented by PD-1 antibody inhibitors, in the field of tumor therapy, scientists have gradually focused on agonist antibody-targeted co-stimulated receptors. Research has proved that agonist antibody targeting co-stimulated receptors is indeed of great significance for the treatment of diseases. In immune regulation, T cell activation requires not only the interaction of antigen-specific T cell receptor (TCR) with antigen peptide MHC molecular complexes on antigen-presenting cells (APC) as the first signal but also co-stimulation as the second signal. Among these co-stimulatory signaling pathways, the B7-CD28 superfamily is one of the co-stimulatory molecule families discovered so far, and its structure is mostly a type I transmembrane glycoprotein belonging to the immunoglobulin superfamily. Currently, many pharmaceutical companies have laid out B7-CD28-based pipelines, which also illustrates the potential value of B7-CD28. Based on our rich field experience and advanced research platform, Creative Biolabs provides comprehensive services to support custom agonistic antibodies and checkpoint agonistic antibodies.

Fig 1. Immune priming between dendritic cell and t cell.

Anti-B7-CD28 Family Agonistic Antibody

CD28, the first co-stimulatory receptor to be discovered, is a founding member of a subfamily of co-stimulatory molecules characterized by extracellular variants of immunoglobulin-like structural domains. CD28 acts primarily as a "second signal" by binding to B7-1/B7-2 on the surface of target cells, lowering the threshold for effective T cell activation and enhancing the "first signal" of T cell activation (MHC-peptide recognition and binding by the T cell receptor (TCR)-CD3 complex to the target cell), which leads to the development of further T cells and their proliferation into immunocompetent cells.

The propensity of B7 family ligands, particularly B7-1 and ICOSLG, to form homodimers at the cell surface facilitates the bivalent binding of a single ligand dimer to two separate CD28 or ICOS dimers at the cell-cell interface of the immunological synapse. The affinity effect of the dimeric B7-1 ligand to bridge to adjacent CD28 or ICOS receptor dimers helps stabilize ligand-receptor interactions, leading to the formation of receptor supramers and subsequently inducing more efficient co-stimulatory receptor signaling. Alternatively, the segregation of CD28 and ICOS receptors within the immune synapse following T cell activation may further contribute to receptor supramer formation and also contribute to efficient co-stimulated receptor signaling in response to B7 ligand binding due to closer proximity to neighboring receptors. The bivalent association of the B7 ligand with CD28 and ICOS suggests that agonist antibodies targeting these receptors must mimic this bridging activity for optimal receptor supramer formation and activation.

Interactions between members of the B7 ligand family and the CD28 receptor family provide co-stimulation or co-inhibition of T cells, modulate T cell activation and tolerance, and are critical for the immune response to foreign pathogens and for appropriate termination of the immune response to prevent inflammation-induced tissue damage. Currently, B7-CD28-based agonistic antibody therapy has played an important role in tumor immunotherapy, autoimmune diseases, and other fields.

Creative Biolabs has a wealth of knowledge and experience in antibody discovery. We would be happy to share with you our knowledge and experience in custom agonistic antibody and premade phage display peptide library screening.

All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

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