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

Informazioni relative al progetto

Repro-TIL

ID dell’accordo di sovvenzione: 101213733

DOI

10.3030/101213733

Data della firma CE 21 Marzo 2025

Data di avvio 1 Giugno 2025

Data di completamento 31 Maggio 2028

Finanziato da

• The European Innovation Council (EIC)

Costo totale

Nessun dato

Contributo UE

€ 2 480 367,37

Coordinato da

ASGARD THERAPEUTICS AB
Sweden

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

Periodo di rendicontazione: 2025-06-01 al 2026-05-31

Sintesi del contesto e degli obiettivi generali del progetto

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.

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

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.

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

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.