ADCs (Antibody-Drug Conjugates) are aptly called “biological missiles” — using antibodies to recognize tumor-cell-surface antigens, precisely delivering highly toxic cytotoxins (“warheads”) into tumor cells, maximizing tumor cell killing while reducing toxicity to normal tissue, addressing traditional chemotherapy’s core problem of collateral damage.
## Three Core Components
**Antibody**: the monoclonal antibody (typically IgG1) recognizing tumor targets. Target selection is critical — high tumor cell expression with low normal cell expression maximizes the therapeutic window. Common targets: HER2 (breast, gastric), Trop-2 (triple-negative breast, urothelial), EGFR, CD19 (B-cell lymphoma).
**Linker**: connects antibody and payload; must remain stable in circulation (no premature release) while releasing payload inside tumor cells. Types: cleavable linkers (triggered by lysosomal proteases, low pH, etc. after cell entry) and non-cleavable linkers. Linker stability directly affects off-target toxicity (premature release) and efficacy (failure to release).
**Payload**: highly active cytotoxins — typically tubulin inhibitors (MMAE, DM1/DM4) or DNA-damaging agents (calicheamicin, camptothecin-derived SN-38, Dxd). First-generation ADCs use DM1/DM4; third-generation uses topoisomerase I inhibitors like Dxd (used in DS-8201) with higher activity.
## Star Drug: DS-8201 (T-DXd / Enhertu)
T-DXd (trastuzumab deruxtecan, Enhertu), developed by AstraZeneca and Daiichi Sankyo, is currently one of the world’s most successful ADCs: targeting HER2, extending median PFS in HER2-positive breast cancer third-line treatment from 5.1 to 25.1 months (DESTINY-Breast03 study); also pioneering new indications in HER2-low breast cancer, significantly expanding the treatable population.
## China’s ADC Track
China’s ADC R&D has entered the global leading tier. RemeGen’s disitamab vedotin (RC48) received FDA Breakthrough Therapy designation. CSPC, Hengrui, and others have multiple ADC pipelines, some completed outbound licensing (license-out) to MSD, Pfizer, and other multinationals at multi-billion dollar deal values — marking global market recognition of China’s innovative drug R&D capability.
See [Synthetic Biology Overview](https://sunqi.org/synthetic-biology-overview-en/) and [CAR-T Cell Therapy](https://sunqi.org/car-t-cell-therapy-en/).
