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

Solid tumors present a significant challenge in oncology due to the limited efficacy of current therapies and resistance to immunotherapies like checkpoint inhibitors. While adoptive cell transfer (ACT) using Tumor-Infiltrating Lymphocytes (TIL) has shown promise in immunogenic tumors like melanoma, broader success has been hindered by inefficient TIL expansion, T-cell exhaustion, and low tumor reactivity (<0.5% tumor-reactive clones in TIL products). These limitations result in inconsistent outcomes and slow clinical adoption.The Repro-TIL project aims to address these challenges by establishing a first-in-class platform designed to selectively expand neoantigen-specific, tumor-reactive TILs. The project builds on the ERC POC project 'NeoIDC,' which introduced a novel method for reprogramming cancer cells into antigen-presenting conventional type 1 dendritic cells (cDC1s), leading to tumor-reactive T cell priming. Repro-TIL approach enhances the production of highly tumor-specific TILs, offering a more effective immunotherapy for solid tumor patients. Repro-TIL will focus on completing preclinical validation and CTA-enabling studies to reach TRL6. The project will optimize the platform for TIL expansion, identify biomarkers of TIL potency, develop a GMP-compliant manufacturing process, and establish regulatory and commercial pathways for future clinical trials and market entry.The project’s multidisciplinary consortium brings together expertise in translational immunotherapy, ACT manufacturing, regulatory strategy, and business development. This combination ensures successful project implementation and lays the groundwork for commercialization. By its conclusion, Repro-TIL will be positioned as a superior ACT solution, with the potential to significantly improve treatment outcomes in melanoma and hard-to-treat solid tumors such as sarcoma and breast cancer. This scalable, cost-effective platform could set the stage for a new era of personalized cancer therapies.