adc-target

B7-H3 is an immune checkpoint-like surface protein found on 60 to 70% of small-cell lung cancers and 80 to 90% of castration-resistant prostate cancers, with little on normal tissue. It is used as an ADC address, chiefly by ifinatamab deruxtecan, now in phase 3 in small-cell lung cancer; whether blocking its immune-dampening role adds anything beyond payload delivery is unresolved.

CD123 is the interleukin-3 receptor alpha chain, present on every blastic plasmacytoid dendritic cell neoplasm and on the blasts and leukaemia stem cells of 70 to 80% of acute myeloid leukaemias. Tagraxofusp and pivekimab sunirine target it in that rare neoplasm, and CAR-T cells against it in AML must spare the normal blood-forming progenitors that also carry it.

CD22 is a B-cell surface protein and the docking site for the leukaemia ADC inotuzumab ozogamicin.

CD30 is a protein on the malignant Reed-Sternberg cells of Hodgkin lymphoma and on some T-cell lymphomas, and the address for the ADC brentuximab vedotin.

CD33 is a myeloid surface marker on the blasts of 85 to 90% of acute myeloid leukaemias and on normal myeloid cells, so drugs against it also hit healthy marrow. It is the target of gemtuzumab ozogamicin, the first ADC ever approved (2000), withdrawn in 2010 and re-approved in 2017 at a lower fractionated dose.

CDH6 is an adhesion protein from kidney development that reappears on ovarian and kidney cancers.

The classic 'CEA' tumour marker measured in blood, also present on the cell surface where ADCs can reach it.

A tight-junction protein normally hidden in the stomach lining that becomes exposed in gastric and pancreatic cancers.

Folate receptor alpha is a vitamin receptor that ovarian cancer cells carry in large numbers, used as the docking site for the ADC mirvetuximab.

A growth-signal receptor. Some cancers make far too much of it, and drugs that block it or use it as a docking site have transformed those cancers.

HER3 is a cousin of HER2 that cancers use as an escape route when HER2 or EGFR are blocked.

Mesothelin is a surface protein on mesothelioma, ovarian, and pancreatic cancers, targeted by ADCs, CAR-T, and T-cell engagers.

A receptor that is either mutated in some lung cancers or amplified as an escape route when other lung cancer drugs fail.

Nectin-4 is an adhesion protein plentiful on bladder cancer cells, used as the docking site for the ADC enfortumab vedotin.

ROR1 is a fetal pseudo-kinase receptor re-expressed on over 90% of chronic lymphocytic leukaemias, 30 to 50% of diffuse large B-cell lymphomas and 40 to 60% of triple-negative breast cancers, and largely absent from healthy adult tissue. Zilovertamab vedotin uses it as an ADC address, in phase 3 in large B-cell lymphoma; whether expression level predicts benefit is unproven.

Tissue factor is a clotting protein that cancers abnormally display on their surface, used as an ADC target in cervical cancer.

TROP2 is a surface glycoprotein present at high levels on most epithelial cancers (breast, lung, urothelial, gastric, pancreatic) and at low levels on normal tissue. It does not drive the cancer; it is a delivery address, used by the approved ADCs sacituzumab govitecan and datopotamab deruxtecan and by sacituzumab tirumotecan, with a TROP2 PET tracer in development to pick patients.