Dr Sona Krajcovicova and colleagues have developed an improved and more scalable method for producing specialised chemical linkers that enable antibodies to be engineered as precise delivery vehicles. The method, recently published in Nature Protocols, could support the development of more consistent and controlled medicines.

Antibodies act like a delivery vehicle, while the payload is the package that needs to be delivered to a specific location. For example, an antibody can recognise a particular marker on a cancer cell and deliver a toxic drug directly to it, helping to limit damage to healthy cells. 

These medicines are known as ADCs (antibody-drug conjugates) are made by joining an antibody to a drug using a chemical connector called a linker. One of the main challenges is to attach the drug without disrupting the antibody’s structure or producing a mixture of molecules carrying different numbers of payloads.

The team’s technology uses Tetra-DiVinylPyrimidine, or TetraDVP, linkers. These linkers are valuable for drug design because they make the structure of the antibody more clearly degined to hold exactly one payload.

Sona explained: “Our TetraDVP technology gives chemists a more controlled way to build the molecular connectors between an antibody and its payload. The linker fastens securely onto the antibody and provides a defined site for attaching one selected molecule. This makes it easier to produce uniform antibody conjugates, which is particularly important when a single cytotoxic drug or another functional payload needs to be introduced precisely.”

ADCs are already used to treat several cancers because antibodies can recognise disease-associated markers and deliver highly potent drugs more selectively. Antibodies can also carry other types of payloads, including imaging probes that help scientists detect and study disease. 

However, conventional attachment methods can produce mixtures: some antibodies may carry several payloads, while others carry fewer or none. This variation can make the resulting medicines more difficult to study, manufacture, compare and optimise.

The TetraDVP method provides a more controlled alternative, producing uniform antibody conjugates with one defined payload. In the future, this precision could help researchers design antibody-based medicines and diagnostic tools whose structures and properties can be adjusted more systematically.

Professor David Spring, the group leader, said: "The value of this work is in the control it offers. By fixing exactly where and how a payload attaches, we turn antibody conjugates into something chemists can engineer systematically rather than empirically – and that is what will allow the next generation of these medicines and diagnostics to be optimised properly. The next step is breadth: applying TetraDVP across a wider range of antibodies and payloads, including imaging agents as well as cytotoxic drugs, and testing how the resulting conjugates behave in more demanding biological settings.”