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Antibody drug conjugates - ADCs


ADCs have been manufactured largely using non-specific, chemical conjugation methods, which result in heteregeneous mixtures with a variety of efficacies and pharmaco-kinetics. Site-specific conjugated antibodies constitute the next generation of ADCs, with a more controlled DAR (drug:antibody ratio) and improved toxicity.

SPLITTERA offers a unique site-specific conjugation technique to produce ADCs. It takes advantage of the fast tras-splicing rates to specifcally couple the desired paylaod to the antibody without including any reduction-oxidation step necessary in other site-specific conjugation methods.

 

 

imagenadc1

The cartoon offers a simplified version of the site-specific conjugation reaction. In practice, the N-intein is fused to mAb chains, while the C-split intein carries the playload. After split intein reaction, each mAb can be conjugated with up to 4 playloads.

REMARKS

• IntN is fused to the mAb at DNA level and recombinantly expressed in the desired host
• IntC can be either chemically synthesized or recombinantly produced
• IntN can be fused to the light chain and the heavy chain of the mAb
• We have a set of non-promiscuous split intein pairs allowing the combination of different payloads in the same ADC