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

Introduction

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.

Project Overview

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.

Objectives

The Repro-TIL approach enhances the production of highly tumor-specific TILs, offering a more effective immunotherapy for solid tumor patients. The project will focus on:

1. Completing preclinical validation and CTA-enabling studies to reach TRL6.
2. Optimizing the platform for TIL expansion.
3. Identifying biomarkers of TIL potency.
4. Developing a GMP-compliant manufacturing process.
5. Establishing regulatory and commercial pathways for future clinical trials and market entry.

Consortium Expertise

The project’s multidisciplinary consortium brings together expertise in:

• Translational immunotherapy
• ACT manufacturing
• Regulatory strategy
• Business development

This combination ensures successful project implementation and lays the groundwork for commercialization.

Conclusion

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.