Breakthrough Neoantigen-specific Tumor-Infiltrating Lymphocyte Therapies Through Novel Dendritic Cell Reprogramming

Projektinformationen

Repro-TIL

ID Finanzhilfevereinbarung: 101213733

DOI

10.3030/101213733

EK-Unterschriftsdatum 21 März 2025

Startdatum 1 Juni 2025

Enddatum 31 Mai 2028

Finanziert unter

• The European Innovation Council (EIC)

Gesamtkosten

Keine Daten

EU-Beitrag

€ 2 480 367,37

Koordiniert durch

ASGARD THERAPEUTICS AB
Sweden

Periodic Reporting for period 1 - Repro-TIL (Breakthrough Neoantigen-specific Tumor-Infiltrating Lymphocyte Therapies Through Novel Dendritic Cell Reprogramming)

Berichtszeitraum: 2025-06-01 bis 2026-05-31

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

Adoptive cell therapy using tumor-infiltrating lymphocytes (TILs) can produce durable responses in some patients with advanced solid tumors, but its broader impact is limited by variable ex vivo expansion, T-cell dysfunction and the low frequency of tumor-reactive clones in the final product. Repro-TIL is developing a next-generation manufacturing approach that transiently converts cells within patient-derived tumor fragments into conventional type 1 dendritic cell-like antigen-presenting cells during the early TIL expansion phase. By presenting the patient's own tumor-antigen repertoire within the native tumor context, the platform aims to enrich functional tumor-reactive T cells without permanently modifying the final TIL product. The project combines biological validation, biomarker discovery, clinical-scale process development, regulatory planning and business maturation to prepare the technology for subsequent clinical development.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

During RP1, the consortium established the ex vivo tumor-fragment workflow and applied it to fresh melanoma samples. Intact tumor fragments were treated with the reprogramming vector and subsequently used for young-TIL outgrowth and rapid expansion. Reprogrammed tumor cells acquired cDC1-like antigen-presentation features, while the resulting TIL products showed improved rapid-expansion performance, increased enrichment of CD8+ T cells and a more favourable activation/exhaustion profile than control products. Autologous functional assays were established to measure T-cell activation, cytokine production and real-time tumor-cell killing. In parallel, samples were generated for single-cell RNA sequencing and paired T-cell receptor analysis to identify expanded clonotypes and biomarkers associated with product quality. Preparatory work also defined the path toward clinical-scale vector and Repro-TIL manufacturing.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

Current TIL manufacturing expands a mixture of tumor-reactive and non-specific bystander T cells and does not actively improve antigen presentation during the earliest phase of culture. Repro-TIL introduces a transient, local antigen-presenting step using the patient's own tumor cells and endogenous tumor-antigen repertoire. Initial results support the potential to increase expansion, enrich CD8+ and tumor-reactive T-cell populations and improve anti-tumor function without permanent genetic modification of the therapeutic T cells. Further uptake will require completion of molecular and functional validation, confirmation of a robust clinical-scale process, GMP-grade vector manufacturRepro-TIL is aligned with European priorities to improve outcomes in cancer, strengthen advanced-therapy innovation and retain manufacturing expertise for personalised medicines in Europe. The project provides evidence that hospital-based TIL manufacturing may be enhanced through a standardised reprogramming step that does not require prior identification of patient-specific antigens or permanent genetic engineering of the final cell product. The emerging policy message is that successful translation of advanced cell therapies benefits from coordinated support for academic-clinical-SME partnerships, shared translational and GMP infrastructure, early dialogue with competent authorities, and funding instruments that bridge preclinical validation, manufacturing scale-up and first-in-human studies.e regulatory scientific advice, pivotal safety and pharmacology studies, and financing for clinical development.