Vascularized Next-Generation Tumor-on-Chip for ADC Global Evaluation

Obiettivo

"Objectives: The project aims to industrialize a human vascularized tumor-on-chip (VANTAGE) to bridge the ""predictive gap"" in Antibody-Drug Conjugate (ADC) development. Primary goals include: (1) Quantifying the ""total spectrum"" of ADC efficacy, from primary tumor regression to the inhibition of micrometastatic seeds; (2) Benchmarking off-target vascular toxicity and barrier using a functional, perfusable microvasculature network; and (3) Standardizing the platform into a regulatory-grade New Approach Methodology (NAM) with reproducibility (CV <10%) suitable for industrial drug filing.

How they will be achieved: We will transition a validated prototype into an injection-molded platform with unidirectional flow, recapitulating vascular-tumor interactions. The platform’s predictive power will be validated through two clinical scenarios: Breast Cancer and NSCLC, monitoring primary mass destruction and secondary colony formation via autonomous biologically driven cell selection. We will benchmark diverse ADC libraries, testing pH-sensitive and Cathepsin-B cleavable linkers to map the interplay between hemodynamics, internalization, and bystander killing. Integration of AI-driven metrics will automate the quantification of vascular morphology and functions alongside metastatic seeding, ensuring objective, high-throughput data.

Relevance to the Work Programme: VANTAGE directly addresses the EIC mandate to develop market-ready NAMs that reduce reliance on animal testing. By providing human-relevant data on vascular toxicity and metastatic bottlenecks—parameters often invisible in CDX/PDX models—it offers a pathway for regulatory-grade adoption. Supported by industry leaders, a former ADC CEO as business advisor, and a regulatory agency, the project maps a clear transition from academic validation to a high-growth spin-off, providing the pharmaceutical industry with a standardized benchmark to de-risk next-generation targeted therapies and reduce clinical attrition."