Antibody-drug conjugates, or ADCs, are antibodies with toxic payloads attached to them. With the antibody acting as a delivery vehicle, payloads like chemotherapy drugs and radioisotopes are then carried directly to the cancer cell.
Many different approaches have been taken to determine the best way to attach, or conjugate, drugs to the antibody. The challenges abound and the debate continues on the ideal method, most appropriate location(s), and optimal amounts to attach to an antibody.
SnAP Optimizes ADC Approach
ADC technologies often use complex chemistry to directly attach a drug via a linker to the antibody. Because early linker technology sought out specific amino acid residues in the antibody sequence, payloads attached in a somewhat random fashion to wherever those residues were found on the antibody. What resulted was an inconsistent mixture with a distribution of various "drug-to-antibody" ratios (DARs) in any given batch. Subsequent developments in linker technology have used various methods, such as insertion of non-natural amino acids into the antibody sequence, to direct their linkers to a specific site, or sites, on the antibody. At the end of the day, complex chemistry, performed on the antibody, is still required to employ these linker technologies.
Our approach is different in a few significant ways. Instead of looking for the best sites on the antibody to attach a linker, the SnAP technology leverages a naturally occurring site tucked in the Fab region of the antibody which a meditope, acting as linker-piece, can snap into. Since there are two Fab regions per antibody, two meditope-enabled sites per antibody can be created—resulting in a consistent "meditope-to-antibody" ratio (MAR) of 2:1. While this is powerful in and of itself, the elegance and simplicity of our "Lego-like" SnAP technology lies in avoiding complex chemistry to attach directly to an antibody. Rather, a payload can easily be attached to the meditope-linker, which in turn snaps into its binding site on the meditope-enabled antibody.