Preclinical Platform for ATMP Evaluation with Patient-Derived Microtumours (PDMs)

Project summary

This project focuses on accelerating the clinical translation and regulatory acceptance of Advanced Therapy Medicinal Products (ATMPs) through the validation of a physiologically relevant, human-based preclinical testing platform. At its core, the project aims to qualify patient-derived microtumours (PDMs) as a robust model system capable of reliably predicting the safety and efficacy of ATMPs in personalized oncology. ATMPs, including CAR-T cells, TCR-T cells, tumour-infiltrating lymphocytes (TILs), and oncolytic AAVs, represent a new generation of highly targeted, individualized therapies. However, their clinical advancement is often delayed by a lack of suitable preclinical models that accurately simulate the tumour microenvironment and immune interactions. The proposed PDM-based co-culture platform addresses this gap by offering a translationally relevant model that mirrors tumour complexity, heterogeneity, and immune contexture. The project will deliver a qualified, data-rich testing platform for the preclinical evaluation of diverse ATMPs. Multimodal readouts, including molecular profiling, functional assays, and immune activity assessments, will generate insights into ATMP mechanisms of action, safety, and tumour-specific responses. These results are expected to significantly enhance regulatory readiness, reduce clinical attrition, and improve personalized treatment strategies while reducing animal based testing.

Our proposal:

- directly supports topics in Health Data and Advanced Therapy Medicinal Products (ATMPs),

- directly contributes to the advancement of Personalized Medicine approaches,

- focuses on a mature technological concept (TRL 6–8) with demonstrated feasibility

- promotes EU-wide consortium building to jointly tackle scientific, regulatory, and translational challenges

- is fully compatible with consortia seeking to develop scalable, cross-border solutions for next-generation cancer therapies.

Key innovation and impact  

This project introduces an innovative approach to preclinical testing of ATMPs by integrating patient-derived microtumours (PDMs) as highly predictive, human-relevant model systems. Unlike conventional in vitro or animal models, our PDMs preserve the native tumour microenvironment, including structural heterogeneity and immune interactions, without artificial matrices. This enables more accurate and physiologically relevant evaluation of next-generation cancer (immuno-)therapies such as CAR-T, TCR-T cells, TILs, and oncolytic viruses. The platform supports high-throughput testing and multimodal analysis, offering a unique advantage in generating translational data for regulatory decision-making. The approach aligns directly with the European Medicines Agency’s (EMA) Regulatory Science to 2025 strategy, which promotes New Approach Methodologies (NAMs) and aims to modernize pharmaceutical development by replacing, reducing, and refining animal testing (3Rs). This alignment increases the potential for regulatory acceptance and supports the ethical advancement of ATMPs in oncology. By establishing PDMs as a qualified preclinical tool for ATMP testing, the project addresses a critical bottleneck in the clinical translation pipeline and provides a scalable solution for more effective, individualized cancer treatments. The current Technology Readiness Level (TRL) of the PDM platform is TRL 6. Through validation, data integration, and regulatory alignment, the project aims to reach TRL 8, enabling broader adoption in clinical and industrial settings.

Need for capacities

To successfully implement the proposed project and ensure its full translational potential, additional capacities in several specific areas would be highly beneficial. These include:

(1) Suppliers of biospecimens, particularly clinical partners or biobanks capable of providing well-annotated tumour biopsies suitable for establishing patient-derived microtumour (PDM) models;

(2) 2 - 3 ATMP developers or suppliers, such as SMEs or research groups working on CAR-T cells, TCR-T cells, TILs, or oncolytic viruses, who could contribute validated therapeutic agents for preclinical testing within the PDM platform, and

(3) experts in single-cell RNA sequencing (scRNA-seq), with the capacity to generate and analyse high-resolution transcriptomic data to characterise tumour heterogeneity and treatment responses.

Inclusion of partners in these areas would significantly strengthen the consortium’s ability to generate clinically relevant data and achieve the project’s scientific and regulatory objectives.