Over the past 30 years, antibody-based anti-cancer therapies have achieved considerable success. Antibody-drug conjugates ( ADCs), a complex and evolving class of drugs, are specifically designed to deliver anti-cancer drugs to cancer cells in the most precise and selectively targeted manner. Currently, with 12 approved drugs on the market, ADCs have become a powerful therapeutic class in oncology and hematology.
(Data source: FDA)
According to the data of Pharmaprojects, there are currently 428 ADC drugs under development. The industry is now focusing on next-generation ADCs with higher efficacy and fewer side effects. HER2 is the most common target for ADC therapy, but the use of other targets is also increasing. Claudin 18 has become a new target for ADC developers.
（Top 5 popular ADC targets）
(Number of ADC licensing transactions in recent years)
An ADC is an enhanced antibody (mAb) designed to exploit the targeting capabilities of monoclonal antibodies by linking them to a cell-killing agent. An ideal ADC has:
A highly selective monoclonal antibody (Antibody) targeting a tumor-associated antigen that has limited or no expression on normal (healthy) cells;
A potent cytotoxic drug ( typically a small molecule with high systemic toxicity) designed to induce target cell death after internalization and release from tumor cells;
Linker that is stable in circulation but releases the cytotoxic agent in target cells.
(Structure of antibody-drug conjugate , Courtesy By Bioconjugator)
Mechanistically, 1. when an intravenously administered ADC binds to a target antigen on the cell surface of a tumor cell, 2. the complex is internalized into the cell. 3. Following internalization, the internalized vesicle fuses with other vesicles and enters the endosomal-lysosomal pathway. 4. Within the lysosome, proteases in the weakly acidic environment digest the monoclonal antibody to release the free payload. 5. The free payload then crosses the lysosomal membrane into the cytoplasm and/or nucleus, where it binds to the target molecule, leading to cell death.
(Data source: Dumontet C, et al. Nat Rev Drug Discov. 2023)
Although the concept of ADC is relatively easy to understand and relatively simple, designing and synthesizing fully functional and effective ADCs is very challenging and usually requires a dedicated development team. Wuhan Mabnus Bio is a company specializing in the development of recombinant proteins and recombinant antibodies. It now has an organic chemistry team that can perform linker chemical conjugation and design for existing antibody drug analogs and provide ADC drug reference materials:
ADC purity test ≥98%:
(SEC-HPLC)
ADC Drug-Antibody Ratio (DAR) Test 3.7:
(HIC-HPLC)
ADC cell endocytosis and toxicity test:
