{"entity":{"id":"idea-bio1-antibody-degrader-conjugates","kind":"idea","name":"Use antibodies to deliver protein-destroying drugs into the right cells","aka":[],"tldr":"Drugs that destroy proteins can hit healthy cells too. Attaching them to an antibody that only docks onto tumour cells would keep them where they are needed.","summary":"Degrader-antibody conjugates replace cytotoxic payloads with a targeted protein degrader, so the payload is only released inside antigen-positive cells. Early programmes target BRD4 and other essential proteins that are too toxic to degrade systemically. This is a route to attack undruggable but essential nuclear proteins that would otherwise be intolerable.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The undruggable drivers): Dang et al., Drugging the 'undruggable' cancer targets (Nature Reviews Cancer 2017)","url":"https://doi.org/10.1038/nrc.2017.36"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["degrader-antibody-conjugate","adc","protac-degrader"],"targets":[],"drugs":[],"companies":["kymera","nurix","sutro-biopharma"],"institutions":[],"pathways":[],"terms":["payload","bystander-effect"],"trials":[],"people":[],"bottlenecks":["b-undruggable-targets","b-toxicity-qol"],"keyPapers":["paper-dang-nat-rev-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A degrader-antibody conjugate produces antigen-dependent degradation of an essential nuclear target in vivo with a therapeutic window at least five-fold wider than the free degrader.","rationale":"ADC linker and payload technology is mature; the constraint on degrading essential proteins is normal-tissue exposure, exactly the problem conjugation solves. Bystander effects may also address antigen heterogeneity.","test":"Compare matched free degrader and conjugate in an antigen-positive versus antigen-negative xenograft pair, with tumour and normal-tissue degradation pharmacodynamics and marrow toxicity as endpoints.","maturity":"preclinical-evidence","actor":"industry","cost":"medium","horizonYears":6},"route":"/ideas/idea-bio1-antibody-degrader-conjugates/","neighbours":{"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"degrader-antibody-conjugate","kind":"technology","name":"Degrader-antibody conjugate (DAC)","route":"/technologies/degrader-antibody-conjugate/"},{"id":"protac-degrader","kind":"technology","name":"PROTACs & molecular glues (targeted protein degradation)","route":"/technologies/protac-degrader/"}],"company":[{"id":"kymera","kind":"company","name":"Kymera Therapeutics","route":"/companies/kymera/"},{"id":"nurix","kind":"company","name":"Nurix Therapeutics","route":"/companies/nurix/"},{"id":"sutro-biopharma","kind":"company","name":"Sutro Biopharma","route":"/companies/sutro-biopharma/"}],"term":[{"id":"bystander-effect","kind":"term","name":"Bystander effect (ADC)","route":"/terms/bystander-effect/"},{"id":"payload","kind":"term","name":"Payload (ADC)","route":"/terms/payload/"}],"bottleneck":[{"id":"b-undruggable-targets","kind":"bottleneck","name":"The undruggable drivers","route":"/bottlenecks/b-undruggable-targets/"},{"id":"b-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"}],"paper":[{"id":"paper-dang-nat-rev-cancer","kind":"paper","name":"Drugging the 'undruggable' cancer targets","route":"/key-papers/paper-dang-nat-rev-cancer/"}]}}