Jerina Hoxha
15.8.25
CERTAINTY consortium outlines blueprint for next-generation digital health tools to support CAR T cell therapy
The CERTAINTY project is proud to announce the publication of a major perspective article in npj Digital Medicine titled “Design specifications for biomedical virtual twins in engineered adoptive cellular immunotherapies”. This work, co-authored by members of the CERTAINTY consortium, presents the foundational framework for creating virtual twins (VTs) tailored to complex, individualised therapies such as CAR T cell treatments.
Background
As cellular immunotherapies like CAR T cells continue to reshape cancer treatment, the need for personalised and predictive decision-support tools has grown. Traditional digital twin models in healthcare are often not equipped to account for the dynamic and individualised nature of therapies based on living cells. Recognising this gap, the CERTAINTY consortium, funded under Horizon Europe, is leading efforts to develop a multi-scale, patient-specific virtual twin that bridges the complexity of both the patient and the cell therapy product.
This paper directly supports the CERTAINTY project’s core mission: to create an interoperable, patient-centric virtual twin for CAR T therapy, enabling better outcomes through precise treatment planning and follow-up care.
Key Points
Minimum Design Specifications for eACI-VTs: The authors define essential components that a virtual twin for engineered adoptive cellular immunotherapies (eACI-VTs) must include. These range from longitudinal single-cell multiomics to organ-level responses and socio-economic variables, enabling a holistic digital representation of the therapy process.
Multi-scale Modelling Framework: The paper introduces a model architecture that spans cellular, intercellular, organ, and whole-body levels, reflecting both the patient’s pathophysiology and the dynamic biology of the CAR T cell product.
Data Standards and Interoperability: Interoperability challenges are tackled through the integration of standards such as OMOP CDM, GA4GH Phenopackets, and FHIR, along with recommendations for future single-cell data standards.
Uncertainty and Validation: The authors identify key credibility risks in VT design, including sparse single-cell data, biomarker validation, and AI/ML integration, and propose robust solutions including federated learning and patient-derived models for calibration.
Clinical & Economic Impact: By simulating patient trajectories and treatment outcomes, eACI-VTs promise to improve patient stratification, reduce adverse effects, and enable performance-based reimbursement models, ultimately contributing to the cost-effectiveness and accessibility of CAR T cell therapies.
Conclusions
This publication provides a critical foundation for advancing the CERTAINTY virtual twin platform and contributes to the broader European efforts under the Digital Europe Programme. By setting the technical and clinical groundwork for VTs in immunotherapy, the CERTAINTY consortium is helping to shape the future of precision oncology and data-driven clinical decision-making. The article also highlights the importance of integrating ethics, gender, and real-world patient diversity into VT design, principles embedded in the CERTAINTY project from its inception.
Access the publication
Read the full open-access article in npj Digital Medicine: https://doi.org/10.1038/s41746-025-01809-6