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Antibody Drug Conjugation
Abzena can undertake the conjugation and analytical characterisation of ADCs in its own laboratories or provide a precursor reagent to its customers to use in-house. In addition to producing ADCs for potential therapeutic use, Abzena can also produce antibody conjugates for diagnostic & imaging purposes and ADCs using standard conjugation technologies for comparative purposes.
Abzena can prepare ADCs using a variety of conjugation technologies including:
ThioBridge™ is Abzena’s proprietary disulfide rebridging linker that delivers more homogeneous ADCs with improved stability. More information is available here.
Abzena can undertake conjugation to the amino acid lysine in monoclonal antibodies (mAb), proteins, and peptides. This type of conjugation can involve one or two step processes. A one-step reaction process can be carried out with a pre-formed linker-drug (usually containing a N-hydroxysuccinimide or other activated ester to react with the antibody) to form the ADC.
In a two-step process, the first step typically involves using a bi-functional reagent (containing both amine- and thiol-reactive functional groups) to react with available ε-amino groups of lysine (i.e., acylation). In the second step, the cytotoxin-linker construct (which possesses a reactive sulfhydryl group) is reacted with the available thiol-reactive groups on the antibody introduced with the linker in step one.
There are currently about 10 ADC candidates that utilize the reactivity of the ε-amino group of lysine in the clinic. Furthermore, one of the two ADCs currently marketed in the United States (ado-trastuzumab emtansine, trade name Kadcyla®) is prepared by conjugation to lysines.
Under controlled conditions, the interchain disulfide bonds of an antibody can be reduced to create sulfhydryl groups that become available for conjugation, while leaving intrachain disulfides intact. Since there are only 4 interchain disulfide bridges in an IgG1, there are only 8 possible sites for conjugation, which is often undertaken using maleimide linkers. One of the two ADCs currently marketed in the United States (brentuximab vedotin, trade name Adcetris®) is prepared by conjugation to reduced cysteines in this way.
Alternatively, antibodies can be engineered with unpaired cysteine residues on each heavy chain that can then be used for conjugation with thiol thiol-reactive linkers to create more homogeneous ADCs with a drug to antibody ratio of two. These engineered antibodies are often referred to as Thiomabs. Abzena has considerable experience in producing ADCs by this approach.
Other Conjugation Methods
Abzena can also perform conjugation using a mixed approach, non-natural amino acid incorporation or Transglutamine based approach.
Working with Abzena
Our services are tailored for each project to ensure that the objectives are met or exceeded. Experienced project teams are assigned to each study focusing on progressing projects through to results in the minimum amount of time. Our clients widely regard us as professional and attentive partners who deliver quality results in a timely manner.
For more information or a quote for our bioconjugation services and technologies contact us.
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