With years of study, Creative Biolabs has established a comprehensive immune checkpoint antibody engineering platform that enables antibody Fc domain optimization to achieve your goal. Our high-quality services will greatly support you in advancing the basic research and clinical applications of cancer immunotherapy.
Antibody Fc Domain Optimization
While antigen binding is undoubtedly a defining feature of any antibody, the Fc domain has evolved to be the true "business end" of an antibody. The Fc domain executes functional interactions with multiple receptors found on almost every cell of the immune system and beyond. The interaction of the Fc domain with a family of receptors of varying affinities on diverse cell types conducts a symphony of immune regulation. IgG Fc receptors such as FcgRI, FcgRIIa, and FcgRIIIa either possess a classic cytoplasmic ITAM (immunoreceptor tyrosine-based activation motif) signaling domain and can stimulate immune effector-cell activation. Therefore, Fc engineering can greatly generate therapeutic antibodies with superior properties relative to their parental native IgG antibodies.
Fig.1 Structure of the Fc region in human IgG. (Kaneko, 2011)
Importance of Immune Checkpoint Antibody Fc Domain Optimization
The development of most immune checkpoint antibody drugs has been a comprehensive understanding of how an antibody engages the patient's immune system via its Fc domain, and in particular, a consideration of how this interaction may be optimized. Anti-CTLA-4 antibody that recognizes cytotoxic T lymphocyte antigen (CTLA-4), was the first approved antitumor immunotherapy to target a regulatory checkpoint receptor. The response of anti-CTLA-4 depends entirely on the expression of the Fcγ receptor (FcγR) in mouse tumor models. What's more, optimizing FcgR binding and antibody-dependent cell-mediated cytotoxicity (ADCC) will result in superior intra-tumoral Treg cell depletion and potent synergy when combined with programmed cell death protein-1 (PD-1) blockade.
Immune Checkpoint Antibody Fc Domain Optimization Service at Creative Biolabs
As a global leader in immune checkpoint antibody discovery and manufacturing, Creative Biolabs provides a range of antibody engineering services for therapeutic antibodies. We are dedicated to offering you first-class immune checkpoint antibody Fc domain optimization services to meet your goal in a timely and cost-effective manner. A variety of Fc optimization techniques are available, including but not limited to Fc domain skeleton optimization and Fc domain glycoengineering optimization.
Immune checkpoint antibody Fc domain skeleton optimization
The two main skeleton optimization approaches are amino acid substitution and exchanging larger amino acid stretches between different isotypes. Variants with altered FcγR binding profiles can be generated and selected for optimal characteristics.
Immune checkpoint antibody Fc domain glycoengineering optimization
IgG antibodies contain a conserved N-glycosylation site on the Fc domain, which attaches a complex, biantennary glycan. The fine structures of this glycan modulate antibody effect functions by affecting the binding affinity of the Fc to Fc receptors.
Creative Biolabs is a leading service provider that focuses on antibody Fc domain optimization for many years. Equipped with advanced platforms and powerful technologies, we can provide high-quality immune checkpoint antibody Fc domain optimization services to exactly suit your demands. If you are interested in our services, please contact us for more details.