ideasIdea
Tumour-on-a-chip with blood flow to test whether big drugs actually get in
Large drugs such as antibody-drug conjugates must cross vessel walls and travel through dense tissue. A chip with flowing channels and human tissue can measure how far they get.
Microphysiological systems with perfusable endothelial channels, stromal fibroblasts and tumour spheroids reproduce interstitial pressure, matrix density and convective transport, the variables that determine ADC, radioligand and nanoparticle penetration. Standard flat cultures and mouse models cannot measure human tissue penetration directly, and penetration is a leading cause of clinical underperformance for large modalities.
Hypothesis
Chip-measured penetration depth and payload delivery rank a set of ADCs in the same order as their observed clinical activity in matched indications.
Rationale
Payload delivered per gram of tumour is a mechanistic determinant of ADC efficacy; the binding-site barrier and stromal exclusion are well described but rarely measured before clinical trials.
What would test it
Benchmark five clinically characterised ADCs with divergent outcomes on a standardised chip and correlate penetration metrics with reported response rates.
Maturity
preclinical evidence
Who has to act
engineering
Cost to try
Small (under $1M)
Years to first evidence
3
Bottlenecks it attacks
- Preclinical models that do not predict people · Nine in ten cancer drugs that work in mice fail in humans. Our models are the reason.