{"entity":{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","aka":[],"tldr":"An antibody-drug conjugate is an antibody that homes to a protein on the tumour cell, is swallowed, and releases a chemotherapy payload inside it. That widens chemotherapy's safe dose window about a hundredfold, which is why payloads too toxic to give alone can be used, though lung inflammation, neutropenia and eye toxicity from the payload still occur.","summary":"Fifteen-plus ADCs are approved. Components: antibody (target, internalisation), linker (cleavable or not, stability), payload (tubulin inhibitors MMAE/DM1; TOP1 inhibitors DXd/SN-38; PBD dimers; calicheamicin), and drug-to-antibody ratio (DAR). Third-generation ADCs (T-DXd, sacituzumab govitecan, Dato-DXd, enfortumab vedotin) with high DAR and bystander-capable TOP1 payloads changed breast, lung, and bladder cancer. Key issues: target heterogeneity, payload cross-resistance, ILD and ocular toxicities, and sequencing multiple ADCs.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Antibody-drug_conjugate","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Antibody-drug_conjugate"}],"tags":[],"related":["idea-efflux-agnostic","idea-neoadjuvant-adc-io"],"cancers":["dlbcl","hodgkin-lymphoma","non-hodgkin-lymphoma"],"sections":["adcs"],"technologies":["topoisomerase-inhibitors","bispecific-adc","dual-payload-adc","degrader-antibody-conjugate","immune-stimulating-adc","masked-adc","site-specific-conjugation","radioimmunotherapy"],"targets":["trop2","her2","her3","nectin4","b7h3","cldn18-2","folr1","tissue-factor","cdh6","met","cd19","bcma","cd33","cd123","ror1","cd79b","cd30","cd22"],"drugs":[],"companies":["celldex","tubulis","adcendo","alentis-therapeutics","bighat-biosciences","callio-therapeutics","cytomx-therapeutics","dantari","emergence-therapeutics","enlaza-therapeutics","firefly-bio","ideaya-biosciences","iksuda-therapeutics","mablink-bioscience","myricx-bio","mythic-therapeutics","nbe-therapeutics","orum-therapeutics","pheon-therapeutics","profoundbio","tallac-therapeutics","valink-therapeutics"],"institutions":[],"pathways":[],"terms":["payload","linker","dar","bystander-effect","ild"],"trials":["aaml0531","luminosity","nct07299747","nct06797999","nct06842498","nct07354711","nct07258407","nct06464055"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["monoclonal-antibody","adc-cdmo-manufacturing","high-potency-payload-synthesis","site-specific-conjugation","sterile-fill-finish"],"notes":["Lymphoma: which antigen can carry a payload is decided by whether it internalises. CD79b is part of a receptor complex that is continuously taken into the cell, and CD30 and CD22 also internalise, so all three carry conjugates; CD20 does not internalise and carries none. The dose-limiting toxicity of the auristatin conjugates used here, polatuzumab vedotin and brentuximab vedotin, is cumulative peripheral neuropathy from the payload rather than anything to do with the antigen."],"principle":"Antigen binding → receptor-mediated endocytosis → lysosomal degradation or linker cleavage → payload release → tumour cell death and, with permeable payloads, killing of neighbouring antigen-negative cells.","generation":"3rd generation dominant; 4th emerging","strengths":["Widens the therapeutic index of chemotherapy 100-fold","Works in 'low' antigen expressers via bystander effect","Active after chemotherapy resistance"],"limitations":["Payload-class toxicities are systemic (neutropenia, ILD, neuropathy, ocular)","Resistance via antigen loss, efflux, TOP1/SLFN11 changes","Manufacturing cost"],"since":2000},"route":"/technologies/adc/","neighbours":{"idea":[{"id":"lymphoma-ev-radiotherapy-free-early-hodgkin","kind":"idea","name":"A radiotherapy-free cure for early Hodgkin lymphoma that actually holds","route":"/ideas/lymphoma-ev-radiotherapy-free-early-hodgkin/"},{"id":"idea-tnbc-adc-sequencing-trial","kind":"idea","name":"A randomised trial of antibody-drug conjugate sequence in metastatic triple-negative breast cancer","route":"/ideas/idea-tnbc-adc-sequencing-trial/"},{"id":"idea-moon-brain-delivery-platform","kind":"idea","name":"A standard platform to get drugs into the brain: focused ultrasound plus shuttle-engineered therapeutics","route":"/ideas/idea-moon-brain-delivery-platform/"},{"id":"idea-post-neoadjuvant-adc","kind":"idea","name":"ADC for residual disease after KEYNOTE-522","route":"/ideas/idea-post-neoadjuvant-adc/"},{"id":"idea-alpha-after-adc","kind":"idea","name":"Alpha radioligands after ADC failure","route":"/ideas/idea-alpha-after-adc/"},{"id":"idea-fund-academic-adc-bispecific-platform","kind":"idea","name":"An open engineering platform for academic ADCs and 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the lowest effective doses of both drugs in a combination, not the highest tolerated","route":"/ideas/idea-tr2-combo-dose-matrix/"},{"id":"idea-bio2-cxcr4-mobilise-then-kill","kind":"idea","name":"Flush dormant cells out of bone marrow, then kill them","route":"/ideas/idea-bio2-cxcr4-mobilise-then-kill/"},{"id":"idea-fus-plus-adc-glioma","kind":"idea","name":"Focused-ultrasound BBB opening to deliver ADCs and radioligands to glioma","route":"/ideas/idea-fus-plus-adc-glioma/"},{"id":"idea-bio1-multi-organ-chip-tox","kind":"idea","name":"Linked human organ chips to predict side effects before people are dosed","route":"/ideas/idea-bio1-multi-organ-chip-tox/"},{"id":"idea-neoadjuvant-adc-io","kind":"idea","name":"Neoadjuvant ADC + IO replacing anthracycline chemotherapy in TNBC","route":"/ideas/idea-neoadjuvant-adc-io/"},{"id":"idea-organoid-guided-adc","kind":"idea","name":"Patient-derived organoids to pick ADC 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reaches trastuzumab deruxtecan","route":"/ideas/idea-tnbc-her2-ultralow-testing-uptake/"},{"id":"idea-tr1-pk-informed-organ-thresholds","kind":"idea","name":"Replace fixed kidney and liver cut-offs with drug-specific, pharmacology-based thresholds","route":"/ideas/idea-tr1-pk-informed-organ-thresholds/"},{"id":"idea-tr1-model-based-dose-finding-with-late-toxicity","kind":"idea","name":"Retire the 3+3: model-based dose finding that counts late and chronic side effects","route":"/ideas/idea-tr1-model-based-dose-finding-with-late-toxicity/"},{"id":"idea-her2-adc-sequencing-payload","kind":"idea","name":"Sequencing HER2 ADCs by payload after T-DXd","route":"/ideas/idea-her2-adc-sequencing-payload/"},{"id":"idea-tr2-smart-sequencing-adc","kind":"idea","name":"Sequential multiple-assignment randomised trials to find the best order of ADCs","route":"/ideas/idea-tr2-smart-sequencing-adc/"},{"id":"idea-tr1-weight-based-vs-flat-dosing-trials","kind":"idea","name":"Test flat versus weight-based dosing of antibodies, and use dose banding to cut waste","route":"/ideas/idea-tr1-weight-based-vs-flat-dosing-trials/"},{"id":"idea-tnbc-brain-metastasis-trials","kind":"idea","name":"Trials that include, and report, brain metastases in triple-negative breast cancer","route":"/ideas/idea-tnbc-brain-metastasis-trials/"},{"id":"idea-trop2-pet-selection","kind":"idea","name":"TROP2 PET to choose and sequence TROP2 ADCs","route":"/ideas/idea-trop2-pet-selection/"},{"id":"idea-bio1-tumour-on-chip-penetration","kind":"idea","name":"Tumour-on-a-chip with blood flow to test whether big drugs actually get in","route":"/ideas/idea-bio1-tumour-on-chip-penetration/"},{"id":"idea-bio1-dual-antigen-adc-escape","kind":"idea","name":"Two-target antibody drugs to close the antigen escape route","route":"/ideas/idea-bio1-dual-antigen-adc-escape/"},{"id":"idea-bio1-antibody-degrader-conjugates","kind":"idea","name":"Use antibodies to deliver protein-destroying drugs into the right cells","route":"/ideas/idea-bio1-antibody-degrader-conjugates/"},{"id":"idea-bio1-slfn11-payload-guidance","kind":"idea","name":"Use SLFN11 status to decide which antibody-drug payload to give next","route":"/ideas/idea-bio1-slfn11-payload-guidance/"},{"id":"idea-bio2-transferrin-shuttle-adc","kind":"idea","name":"Use the brain's own transport door to carry antibody drugs across","route":"/ideas/idea-bio2-transferrin-shuttle-adc/"}],"cancer":[{"id":"all-leukemia","kind":"cancer","name":"Acute lymphoblastic leukaemia","route":"/cancers/all-leukemia/"},{"id":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"aml-paediatric","kind":"cancer","name":"Acute myeloid leukaemia in children","route":"/cancers/aml-paediatric/"},{"id":"advanced-stage-classical-hodgkin-lymphoma","kind":"cancer","name":"Advanced-stage classical Hodgkin lymphoma (stage III to IV)","route":"/cancers/advanced-stage-classical-hodgkin-lymphoma/"},{"id":"alk-negative-anaplastic-large-cell-lymphoma","kind":"cancer","name":"ALK-negative anaplastic large cell lymphoma","route":"/cancers/alk-negative-anaplastic-large-cell-lymphoma/"},{"id":"alk-positive-anaplastic-large-cell-lymphoma","kind":"cancer","name":"ALK-positive anaplastic large cell lymphoma","route":"/cancers/alk-positive-anaplastic-large-cell-lymphoma/"},{"id":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/"},{"id":"bpdcn","kind":"cancer","name":"Blastic plasmacytoid dendritic cell neoplasm (BPDCN)","route":"/cancers/bpdcn/"},{"id":"cervical","kind":"cancer","name":"Cervical cancer","route":"/cancers/cervical/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"egfr-mutant-nsclc","kind":"cancer","name":"EGFR-mutated non-small-cell lung cancer","route":"/cancers/egfr-mutant-nsclc/"},{"id":"endometrial","kind":"cancer","name":"Endometrial cancer","route":"/cancers/endometrial/"},{"id":"extensive-stage-sclc","kind":"cancer","name":"Extensive-stage small-cell lung cancer","route":"/cancers/extensive-stage-sclc/"},{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"her2-amplified-colorectal","kind":"cancer","name":"HER2-amplified colorectal cancer","route":"/cancers/her2-amplified-colorectal/"},{"id":"her2-mutant-nsclc","kind":"cancer","name":"HER2-mutant non-small-cell lung cancer","route":"/cancers/her2-mutant-nsclc/"},{"id":"breast-her2-positive","kind":"cancer","name":"HER2-positive breast cancer","route":"/cancers/breast-her2-positive/"},{"id":"hodgkin-lymphoma","kind":"cancer","name":"Hodgkin 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