Immunoglobulin (Ig) G is the major antibody of the secondary immune response and has the longest half-life of the five immunoglobulin classes (IgA, IgD, IgE, IgG, and IgM) due to recycling by the neonatal Fc receptors (FcRn). Because lacking protection by FcRn, some shortcomings of the short half-life of non-IgG antibodies largely limit their potential for application, such as rapid blood clearance, rapid shedding rates, and poor retention times on targets (e.g., tumors). At present, Creative Biolabs is glad to introduce the antibody half-life extension service for non-IgG antibodies to improve stability and performance.
Introduction to Antibody Half-life
Half-life is the average survival time after the formation of antibody molecules, usually expressed as the time required to remove 50% of the known amount of immunoglobulin from animal bodies. In clinical applications, a short serum half-life increases the potential of applications and the doses of therapeutic agents. With the consistent growth of therapeutic antibodies in the global market, many efforts have been made to improve the engineering, safety, and efficacy of therapeutic antibodies, among which, stability is one of the key issues often discussed in the preclinical development process. Increasing the half-life of therapeutic antibodies has several benefits, ranging from higher therapeutic efficacy to increased patient compliance, which all result in fewer treatment cycles and lower costs. Considering these convincing benefits, developers often improve the stability of the antibodies by appropriately prolonging the half-life after identifying the specific therapeutic antibodies they need.
Strategies of Half-life Extension for Non-IgG Antibodies
Antibody therapy is an effective method for the treatment of various malignant tumors. The overwhelming majority of current clinical therapeutic antibodies are IgG isotypes. However, not all patients respond to this treatment and some may suffer relapses. Recently, the important roles of non-IgG antibodies in certain diseases have been revealed, which greatly drives the exploration and development of non-IgG antibody engineering.
Both IgG antibody and non-IgG antibodies display a high level of species-specificity not only in target binding through the variable region, but also in the Fc region which is vital in maintaining long term stability. The glycosylation of non-IgG antibodies is closely related to their pharmacokinetic and pharmacodynamic (PK/PD) properties, suggesting that glycoengineering strategies may improve their therapeutic efficacy, which is probably related to prolong the retention time in vivo. As non-IgG antibodies lack a binding site for FcRn, C-terminal fusion of human albumin or FcRn-binding motifs to non-IgG antibodies, and the construction of non-IgG hybrid antibodies are viable ways to increase the half-life of antibodies. Empowering non-IgG antibodies with albumin-binding capacity also results in in vitro and in vivo functional antibodies with enhanced exposure and prolonged half-life. Therefore, glycoengineering strategies or the combination of these novel approaches may further enhance the serum half-life and therapeutic efficacy of non-IgG antibodies.
Fig.1 Several strategies of half-life extension for antibodies. (van Witteloostuijn, 2016)
With years of experience in antibody engineering and our most devoted scientists, Creative Biolabs has gained significant knowledge in antibody fragments engineering. We are confident in delivering you an optimized non-IgG antibody with a desirable half-life that can meet your specific applications. If you are interested in our service, please do not hesitate to contact us for more details.
- van Witteloostuijn, S.B.; et al. Half-life extension of biopharmaceuticals using chemical methods: alternatives to PEGylation. ChemMedChem. 2016, 11(22): 2474-2495.
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