ANITBODY-DRUG
CONJUGATES
ADC Proposed Mechanism of Action:1-3
As shown in the figure below, ADCs are engineered to have the antibody (1) track a specific tumor antigen and bind themselves to the surface of cancer cells and; upon internalization (2) and processing within endosomes or lysosomes, the ADC drug then releases its lethal cargo (3) leading to tumor cell death (4).
Opportunities for ADCs1
- Next Generation Payloads: Payloads with improved therapeutic index or novel mechanism of action
- New Linkers: : Optimized linkers generating stable ADCs with good drug-like properties
- Target Engine: Identify antigen targets with tumor or tissue selectivity and ability to internalize ADCs
- Optimized Biologics: Novel formats to improve tumor delivery or reduce toxicity
- Controlled Drug Loading: Generate more uniform drugs, improve pharmacokinetic properties, optime drug-to-antibody ratio to maximize therapeutic index
Therapeutic Potential
Treating cancer with cytotoxic agents introduces a risk of systemic adverse events.
Binding of the ADC to the recognized antigen triggers internalization and degradation of the mAb, which releases the cytotoxin inside the cell.
Ideally, ADCs may help provide a wider therapeutic index with potentially fewer side effects than "free" cytotoxic agents.
Relevant Targets
- Bouchard H, Viskov C, Garcia-Echeverria C. Antibody-drug conjugates—a new wave of cancer drugs. Bioorg Med Chem Lett. 2014;24(23):5357-5363.
- Peters C, Brown S. Antibody-drug conjugates as novel anti-cancer chemotherapeutics. Biosci Rep. 2015;35(4):e00225. doi: 10.1042/BSR20150089.
- Diamantis N, Banerji U. Antibody-drug conjugates—an emerging class of cancer treatment. Br J Cancer. 2016;114(4):362-367.