{"entity":{"id":"masked-adc","kind":"technology","name":"Masked / conditionally active ADC","aka":[],"tldr":"An ADC wearing a mask that only comes off inside the tumour, so it ignores the same protein on healthy tissue.","summary":"Probody platform (CytomX; praluzatamab ravtansine CD166, CX-2051 EpCAM with TOP1 payload showing responses in colorectal cancer in 2025) and protease-activated designs allow targeting of antigens that are also expressed at high levels on normal tissue (EGFR, EpCAM, CD71). Also 'tumour microenvironment-activated' linkers cleaved by extracellular proteases.","status":"phase-2","asOf":"2026-09-04","links":[{"label":"Autio et al., Probody therapeutics: an emerging class of therapies designed to enhance on-target effects with reduced off-tumour toxicity (Clinical Cancer Research 2020)","url":"https://doi.org/10.1158/1078-0432.CCR-19-1457"}],"tags":["frontier"],"related":[],"cancers":[],"sections":["adcs"],"technologies":["adc"],"targets":[],"drugs":[],"companies":["cytomx-therapeutics","synsorybio"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-autio-clin-cancer-res"],"journals":[],"dependsOn":[],"notes":[],"principle":"Peptide mask blocks antigen binding until cleaved by tumour-enriched proteases (MMPs, uPA, legumain).","generation":"4th (next-gen)","strengths":["Unlocks targets previously too toxic","Wider therapeutic index"],"limitations":["Incomplete masking; protease heterogeneity"]},"route":"/technologies/masked-adc/","neighbours":{"section":[{"id":"adcs","kind":"section","name":"Antibody-Drug Conjugates","route":"/fronts/adcs/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"dna-origami-nanorobots","kind":"technology","name":"DNA origami nanorobots","route":"/technologies/dna-origami-nanorobots/"},{"id":"logic-gated-therapeutics","kind":"technology","name":"Logic-gated therapeutics (AND, NOT gates)","route":"/technologies/logic-gated-therapeutics/"}],"company":[{"id":"cytomx-therapeutics","kind":"company","name":"CytomX Therapeutics","route":"/companies/cytomx-therapeutics/"},{"id":"synsorybio","kind":"company","name":"SynsoryBio","route":"/companies/synsorybio/"}],"paper":[{"id":"paper-autio-clin-cancer-res","kind":"paper","name":"Probody Therapeutics: An Emerging Class of Therapies Designed to Enhance On-Target Effects with Reduced Off-Tumor Toxicity for Use in Immuno-Oncology","route":"/key-papers/paper-autio-clin-cancer-res/"}],"roadmap":[{"id":"adc-generations","kind":"roadmap","name":"ADC roadmap: from Mylotarg to bispecific and dual-payload ADCs","route":"/roadmaps/adc-generations/"}],"idea":[{"id":"idea-bio2-tumour-anchored-tgfbeta-trap","kind":"idea","name":"Anchor a TGF-beta trap in the tumour stroma so it cannot act everywhere","route":"/ideas/idea-bio2-tumour-anchored-tgfbeta-trap/"}],"term":[{"id":"prodrug","kind":"term","name":"Prodrug","route":"/terms/prodrug/"}]}}