Antibody drug conjugates (ADCs) have been gaining momentum in recent years, with four FDA-approved drugs currently on the market and many more in clinical and preclinical development. In a newly published study, scientists at the Scripps Research Institute describe a new class of ADCs that use a “double decker” technology to tie antibodies and a drug together, producing potent cancer therapies. According to the researchers, this new configuration will make ADC design easier and further propel this emerging class of drugs forward.
The paper was published yesterday in Nature.
The name for the new technology is dual variable domain antibody-drug conjugates or DVD-ADCs. These DVD-ADCs combine a cancer-targeting antibody with a catalytic antibody that carries the drug.
In animal models of HER2-driven breast cancer and multiple myeloma and non-Hodgkin lymphoma, the DVD-ADCs proved to be effective against all three cancer types.
One of the main advantages of this technique is the relative ease by which the ADCs can be produced. The DVD-ADCs take advantage of an unusually reactive lysine residue of the catalytic antibody. Drugs can be tied to this residue with high precision and stability, allowing for one-step preparation of homogenous ADCs. With this method, efficiency of drug conjugation can be precisely monitored with a catalytic assay.
Another advantage is that antibody purification can be performed after the ADC is assembled, rather than during initial production, potentially making manufacturing easier.
"The advantage is we can produce ADCs at a fast rate in a single step," said graduate student Alex Nanna, first author of the study. "The DVD-ADC format brings everything together in a very efficient way."