Targeting with specific antibodies
Antibody-Drug Conjugates (ADCs) represent an innovative therapeutic application combining the favourable selectivity, stability and pharmacokinetic profiles of monoclonal antibodies with the potent antitumor activityof highly cytotoxic small-molecule drugs. Unlike traditional chemotherapy, ADCs are designed to target and kill only the cancerous cells while sparing healthy tissues.
Killing cancer with efficient cytotoxic drugs
Once an ADC is bound to its specific extracellular antigen target, the cancer cell internalizes the molecule by endocytosis. The resulting early endosome is then driven through the microtubule tracks and ultimately fuses with lysosome once next to the perinuclear space. Proteolytic enzymes perform degradation of the ADC-Marker couple, including the antibody and the linker, which subsequently releases the potent drug payload. The drug can then diffuse throughout the cell and exert its cytotoxic activity.
Decreasing the doses
Today the challenge lies in developing linkers with two apparently opposite features:
- resistance to physiological and physicochemical constraintes of the patient’s organism,
- sensibility to proteolytic enzymes of lysosomes to release the payload.
Improving the therapeutic index of ADCs
- improving the drug-linker design (improved plasma stability, use of enzyme-cleavable moiety ar lack thereof, use of new payloads with new mechanisms of action, improved payload protection against metabolism.
- improving ADC physicochemical and pharmacological parameters (improved drug-loading, increased overall hydrophilicity, improved pharmacokinetics, decreased non-specific uptake).
- improving the antibody component (new tumor targets, bispecific antibodies boosting the endocytosis step, Fc region removal to reduce non-specific interactions) or using an antibody mimetic as targeting unit (nanobodies, therabodies, affibodies…
Our solution: our ADC platform
Our drug-linker technology aims to address all these considerations by delivering ADCs that:
- have an increased drug loading capacity (DAR of 8-16) without negative impact on aggregation and/or pharmacokinetics,
- are homogeneous and plasma-stable,
- have improved hydrophilicity and pharmacokinetics profiles,
- are easier to develop and produce since our technology is directly applicable to any monoclonal antibody with no re-engineering required nor tedious enzymatic coupling procedures.
Our platform is modular and readily applicable to any conventional or next-generation toxic payload. The platform can be paired with enzyme-cleavable moieties (Val-Cit, Val-Ala, glucoronide triggers…) or can be used in non-cleavable linker designs (when the final proteolytic degradation of the ADC is predominantly held responsible for the release of the toxic payload).