- Research Services
- Antibody Discovery
- Antibody and Protein Engineering
- Cell Line Development
- Development & Manufacturing
- Investor Relations
- Contact Us
ThioBridge™ Conjugation Technology
Abzena has developed its ThioBridge™ technology to efficiently conjugate drugs to antibodies to create less heterogeneous ADCs with better stability. The technology links drugs to the naturally occurring interchain disulfide bond of antibodies. The disulfide bonds are first reduced but, unlike conjugation using maleimide chemistry, the bond is re-bridged as part of the conjugation process thereby stabilising the tertiary structure of the antibody.
The ThioBridge™ conjugation process can be optimised to consistently produce an ADC with a very high (around 90%) conversion to an ADC with one drug attached across each of the four reduced disulfide bonds. This results in an ADC with an antibody drug ratio of four (DAR 4) without requiring any re-engineering of the antibody for conjugation.
Application of ThioBridge™
ThioBridge™ can be used to attach a range of payloads using either cleavable or non-cleavable linkers to an antibody or other targeting molecule with accessible disulfide bonds. The technology has been applied to a variety of antibodies with different targets and a range of different types of smaller targeting molecules, including antibody fragments.
Benefits of ThioBridge™
ThioBridge™ ADCs can be reproducibly produced at lab scale with a very high conversion to DAR4. A ThioBridge™ brentuximab ADC that otherwise contained the same components as Adcetris® was produced and was shown to be primarily DAR 4 as opposed to the more heterogeneous Adcetris®.
Above: Analytical Hydrophobic Interaction Chromatography (HIC) of Adcetris® and a crude ThioBridge™ brentuximab MMAE DAR 4 conjugation mixture.
ThioBridge™ ADCs maintain excellent stability in sera. Adcetris® showed a significant alteration in DAR species over a 7 day period in comparison to a ThioBridge™ ADC.
Above: Stability of purified Adcetris® DAR 4 and ThioBridge™ brentuximab MMAE DAR 4 conjugate in IgG depleted human serum. Both ADCs were incubated at 37 °C for 7 days. Changes in the DAR distribution were monitored by HIC.
ThioBridge™ is compatible with a wide range of payloads including auristatins (MMAE, MMAF), maytansines and DNA alkylating agents.
Better in vivo
The homogeneity and stability advantages of ThioBridge™, as well as Abzena’s expertise and experience in developing effective ADC reagents, results in more efficacious ADCs in vivo. A ThioBridge™ trastuzumab MMAE ADC was compared to the marketed ADC, Kadcyla®. In in vivo studies the ThioBridge™ ADC showed a significant reduction in tumour volume compared to Kadcyla® after a single dose.
Above: Mean tumour volume over time for and Kadycla® in a JIMT-1 xenograft model and ThioBridge™ trastuzumab MMAE.
Working with Abzena
Abzena has applied ThioBridge™ to produce better antibody drug conjugates (ADCs) using whole antibodies, novel antibody formats and antibody fragments and have access, via our partners, to a range of cytotoxic drugs with different mechanisms of action. We collaborate with a wide range of organisations from virtual companies through to big pharma, including many of the world’s top companies, as well as academic research groups from across the globe.
To get more information, a quote or to schedule a teleconference please contact us.