Antibody-Drug Conjugates (ADCs) are highly potent biopharmaceuticals that use the targeting ability of monoclonal antibodies to selectively bind to tumor cells where the conjugated cancer drug is released. The antibody and the small molecule drug are bound by a linker. Only when the linker is cleaved do these cell-killing drugs become active. This generates an excellent control mechanism of drug activation, allowing an increase of the therapeutic window and thereby the use of highly potent drugs. Current ADC technologies rely on biological cleavage of the linker. The ADC has to bind to a tumor cell-specific membrane receptor and subsequently be internalized in the tumor cell for cleavage of the linker – and thus activation of the drug – to occur. As the number of tumor-specific receptors that ensure efficient internalization is limited, especially in solid tumors, a wide range of cancer-targets remains out of reach of ADCs.
Antibody-Drug Conjugates – Our Proprietary Solution
Tagworks tackles this problem by focusing on chemically triggered release mechanisms for ADCs. Recently, we succeeded in modifying the fastest and highly selective click reaction, the inverse-electron-demand-Diels-Alder reaction, in such a way that we achieved selective bioorthogonal release. An unprecedented approach that holds great promise for employing chemically triggered release of a drug from a tumor-bound ADC. This would mean a substantial expansion of the scope of suitable ADC targets to include for example slow- or non-internalizing targets and extracellular-matrix constituents that are not suitable for biological cleavage mechanisms.
- ADC linker that can be cleaved in vivo by adminstration of a chemical probe
- Based on modification of established and in vivo validated Tagworks pretargeting technology
- Well suited for ADC’s based on antibody fragments (2-step procedure), or based on full antibodies in combination with a clearing agent (3-step procedure)