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BOC Sciences provides comprehensive strategies for antibody-drug conjugate (ADC) to our customers worldwide. We possess the most advanced equipment and unique R&D expertise to provide personalized antibody coupling services according to customers' specific needs promptly. Moreover, we monitor our products according to strict quality control standards during development and optimization processes to ensure our customers receive first-class services and products.
The development of ADCs has been accelerated worldwide in recent years, and this novel biotechnological drug is a potent anticancer agent and also considered an essential disease treatment. The complex structure and a high degree of heterogeneity of ADC pose significant challenges for structural characterization. Among them, the determination of the drug-to-antibody ratio (DAR), drug conjugation site, and conjugation ratio are relatively complicated. BOC Sciences' ADC solution platform will help you solve these problems and challenges.
Fig. 1. Key structures and action mechanisms of ADCs.
Depending on the reaction site, conjugation strategies can be divided into non-specific conjugation by native residues or site-specific conjugation by genetic engineering sites and UV cross-linking. Non-specific conjugation techniques include lysine conjugation and cysteine conjugation, which are classical and mature, without the need to introduce unnatural amino acids. Site-specific conjugation can enhance the site-specificity of ADC conjugation by altering the amino acid sequence and introducing a reactive handle, including enzymatically modified antibodies. Enzymatically modified antibodies enable enzyme-chemical two-step efficient site-directed conjugation, so certain enzymes recognize specific amino acid tags. Nevertheless, unnatural amino acids conjugation can introduce special groups to facilitate efficient specific conjugation reactions.
ADC is considered to be a critical and promising anti-tumor biotechnological drug. Up to date, fourteen conjugates have been approved by regulatory agencies for cancer treatments. According to the antibody's characteristics and our customer's specific requirements, BOC Sciences can propose the most appropriate coupling strategy to achieve the ADC you are interested in.
IgG is a glycoprotein. It contains an N-glycan at the N297 position of the Fc fragment in each heavy chain's CH2 domain, in which the glycosylation site can be used as an attachment point for the payload. The long-distance positioning between the polysaccharide and the Fab region reduces the risk of damaging the antigen-binding ability after conjugation. In addition, the different chemical compositions between N-glycan and peptide chains allow site-specific modification and are suitable for coupling. BOC Sciences can develop various strategies for bioconjugation through the carbohydrate portion of antibodies.
There are only 8 free cysteines on each antibody that can be connected to the linker through disulfide bonds. Due to the limited number of binding sites and the unique reactivity of the thiol group, using cysteine as the linking site can reduce the ADCs heterogeneity. BOC Sciences has built a comprehensive, state-of-the-art technology platform that provides customized antibody-drug conjugate (ADC) services using cysteine conjugation.
One of the most common conjugation methods applies lysine residue, in which the amino acid nucleophilic NH2 group reacts with the payload's electrophilic N-hydroxysuccinimide (NHS) group. Despite the simplicity of this reaction, the high abundance of available lysine residues can cause ADCs to form inhomogeneous mixtures under random distribution. Thus, DAR is strictly controlled in this method to ensure drug/antibody stoichiometric ratio. BOC Sciences can perform lysine conjugation with an appropriate DAR value to develop antibody-drug conjugates (ADC).
By introducing β-acetylphenylalanine as an unnatural amino acid residue in the antibody supported a ketone group that is not present in natural amino acids. Thus, an oxime bond can be formed between the ketone group and the alkoxyamine, which is highly stable under physiological conditions. BOC Sciences can synthesize site-specific antibody-drug conjugate (ADC) according to your research needs using unnatural amino acids that contain orthogonal chemical reactivity.
BOC Sciences also provides other conjugation methods, including enzymatic modification of antibodies. The payload attachment can be achieved selectively by inserting specific amino acid tags in the antibody sequence. Then, these tags are recognized by specific enzymes, such as formylglycine-generating enzyme (FGE), microbial transglutaminase (MTG), transpeptidase or tyrosinase, and enabling site-specific conjugation.
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