Challenges and limitations of ADC development
One of the major challenges of modern medicine is to find a safe cancer therapy. The Food and Drug Administration has approved Adcetris® (brentuximab vedotin) and Kadcyla® (ado-trastuzumab emtansine) that are considered as powerful treatments against cancer. They are good examples of antibody-drug conjugates (ADCs). The principle is to link a drug, that can be cytotoxic, to an antibody able to target cancer cells. Unfortunately, the development of ADCs faces some difficulties. Indeed, depending on the method for the conjugation, the ADC can be highly heterogenous.
A simple and robust conjugation, 4FB linker to HyNic linker
As used by Rongsheng E. Wang et in 2015, the S-4FB linker can be used to generate antibody conjugate HLCX-dasatinib (doi:10.1021/jacs.5b00620). Since that first step, more improvement were made. Indeed, we can combine the S-4FB to HyNic-biomolecules. The conjugation is simple, rapid and stable. Trilink Biotechnologies provides that technology under the label ChromaLink. The principle is illustrated on the picture below.
There is also a cleavable S-4FB linker and a MHPH (Maleimide HyNic) crosslinker for maleimide-based ADCs.
ChromaLink technology allows:
- Rapid and efficient conjugation (>80%)
- Simple quantification of the conjugate by simple UV scan
- High stability (pH2-100, 95°C)
- Preserves activity of the drug or the enzyme
- Reproducibility and ADC homogenous population
So it allows also drug conjugation to oligonucleotides such as aptamers for another type of cell targeting.
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