# Masked / conditionally active ADC

Source: https://onco.cc/technologies/masked-adc/  
OnCo record `masked-adc` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Technology
- Status: phase-2
- Last checked: 2026-09-04
- Tags: frontier
- 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

## Sources

- 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): https://doi.org/10.1158/1078-0432.CCR-19-1457

## Connected records

- fronts: [Antibody-Drug Conjugates](https://onco.cc/fronts/adcs/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/), [DNA origami nanorobots](https://onco.cc/technologies/dna-origami-nanorobots/), [Logic-gated therapeutics (AND, NOT gates)](https://onco.cc/technologies/logic-gated-therapeutics/)
- companies: [CytomX Therapeutics](https://onco.cc/companies/cytomx-therapeutics/), [SynsoryBio](https://onco.cc/companies/synsorybio/)
- key papers: [Probody Therapeutics: An Emerging Class of Therapies Designed to Enhance On-Target Effects with Reduced Off-Tumor Toxicity for Use in Immuno-Oncology](https://onco.cc/key-papers/paper-autio-clin-cancer-res/)
- roadmaps: [ADC roadmap: from Mylotarg to bispecific and dual-payload ADCs](https://onco.cc/roadmaps/adc-generations/)
- ideas: [Anchor a TGF-beta trap in the tumour stroma so it cannot act everywhere](https://onco.cc/ideas/idea-bio2-tumour-anchored-tgfbeta-trap/)
- terms: [Prodrug](https://onco.cc/terms/prodrug/)

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