NexMab™ ADC Technology
Technology
As many global pharmaceutical companies are currently developing anti-cancer drugs, an ideal anti-cancer drug is a targeted therapy, which selectively tracks and removes cancer cells while it does not affect healthy cells.
As a targeted therapy, antibody-drug conjugate (ADC) utilizes antibody as a carrier, delivering highly cytotoxic compounds to cancer cells specifically. The highly cytotoxic payloads are connected to antibody via chemical linkers. The chemistry of the linker determines the characteristic of ADC.
Using NexMab™ ADC technology, Alteogen is developing multiple anti-cancer drugs as the second-generation ADCs.
* Highly selective on cancer cells
* Powerful anti-cancer therapeutic effect
Uniqueness
The first generation of ADC, including Adcetris® and Kadcyla®, employed site-nonspecific conjugation methods and the payloads are conjugated to cysteines of interchain disulfide bonds (Adcetris) or lysines (Kadcyla). But higher stability and efficacy of ADC require site-specific conjugation and many companies are endeavoring to develop a next generation ADC technology by employing site-specific conjugation method.
In NexMab™ ADC technology, metal ion binding motif is used for site-specific conjugation. C-terminal introduced metal ion binding motif could protect the cysteine residues during the oxidation process by coordinate bond with metal ion. Conventional cysteine conjugation method demands a reduction of cysteine residues to increase the conjugation yield. But use of reducing agents, DTT or TCEP, inevitably leads to non-specific conjugation to the cysteines of disulfide bonds. But, in NexMab™ ADC technology, those reduced cysteines of disulfide bonds could be selectively oxidized while the cysteines in NexMab™ peptides are protected from oxidation by participating metal ion coordination, enabling a site-specific conjugation.