Creative Biolabs is one of the world’s most trusted experts for bispecific antibody (BsAbs) development and production. Based on our vast experience gained from developing hundreds of antibodies, we offer high quality antibody-functionality conjugates with high affinity and low immunogenicity for both academic and clinical purposes.
Chemical conjugation is a versatile strategy that allows the generation of several different formats of BsAbs by using different crosslinkers. The crosslinkers contain several reactive groups which are used to conjugate the antibody units. Moreover, if there are additional reactive groups, they can be used to incorporate more functionalities such as fluorophores, simulating peptides, PEG, siRNA, cytotoxic drugs, etc. Different from antibody-peptide conjugates in which the antibody portion just act as carrier, antibody-functionality conjugates retain the reactivity of antibody moieties and the property of additional functionalities. The strategy has been widely used is the PEGylation of proteins. As antibody fragments, the small size of scFv and Fab endow them with several advantages including a better tissue penetrance. However, they have shorter half-life. To overcome this problem, PEGylation is an optional strategy to extend the molecule half-life and has also been clinically proven in marketed products.
Figure 1. Schematic diagram of antibody-functionality conjugates.
ScFv1-PEG-scFv2 BsAb is also such a kind of BsAb that consists of two scFvs targeting two different antigens and a cross-linker containing PEG. Thus, this type of BsAb has three reactive groups, two scFv reactive groups and a PEG. The introduction of PEG into cross-linker has many advantages. Firstly, the risks of inactivating the antibody and the heterogeneity of the product are reduced due to its site-specific manner. Furthermore, it can extend the antibody’s half-life. Researchers have successfully developed several scFv1-PEG-scFv2 BsAbs. For example, one of the reported scFv1-PEG-scFv2, AZ17, is a BsAb combining scFvs targeting both IL-23 and IL-6. The scFvs are formed in E.coli and connected by a PEG molecule to increase stability and extend pharmacokinetics. Two relevant preclinical in vivo mouse models have exhibited that this antibody can effectively neutralizes both IL-23 and IL-6 simultaneously with great potency and alleviates psoriatic parameters.
With our well-established recombinant and chemically conjugated antibody generation platforms, the experienced scientists here at Creative Biolabs are dedicated to help you develop unique antibody-functionality conjugates. We also provide other various services regarding BsAbs development. Please feel free to contact us for more information and a detailed quote.
References
1. Stenderup, K.; et al. AZ17: a new bispecific drug targeting IL-6 and IL-23 with potential clinical use—improves psoriasis in a human xenograft transplantation model. Protein Engineering, Design and Selection. 2015, 28(10): 467-480.
2. Schellinger, J. G.; et al. A general chemical synthesis platform for crosslinking multivalent single chain variable fragments. Organic & biomolecular chemistry. 2012, 10(8): 1521-1526.
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