Consortium Partners

Collaborators (not funded): University of Applied Sciences Northwestern Switzerland (Oya Tagit), Medical University of Vienna (Alberto Benazzo)

Project Overview

SAIL develops innovative nanotechnology-based immunotherapy targeting myeloid cells to treat both cancer and chronic transplant rejection. The project exploits polylactic-co-glycolic acid (PLGA) nanoparticles loaded with microRNAs (miR-146a and miR-155 agonists/antagonists) to reprogram immune responses in opposite clinical settings that share common molecular mechanisms.

Main Goals

• Reprogram myeloid cells via miRNA-loaded PLGA nanoparticles to inhibit immune suppression in cancer and promote it in transplantation
• Optimize nanoparticle formulations for selective myeloid cell targeting with enhanced biodistribution and pharmacokinetics
• Evaluate efficacy in in vitro, ex vivo (patient-derived samples), and in vivo (mouse models) systems
• Perform comprehensive transcriptomic and epigenetic profiling to identify regulatory networks
• Assess biocompatibility and toxicity through standardized testing protocols
• Advance to GMP-grade production and prepare investigational medicinal product dossier for Phase I clinical trials
• Establish regulatory pathway for clinical translation in collaboration with European regulatory authorities

Scientific Approach

The consortium leverages preliminary data showing that PLGA nanoparticles efficiently deliver microRNAs to myeloid cells, modulating their immunosuppressive activity. In cancer, antagonist-miRNAs reprogram tumor-associated myeloid cells to restore anti-tumor immunity. In transplantation, agonist-miRNAs enhance immunosuppressive properties to prevent chronic allograft dysfunction (CLAD).

Work Packages

• WP1: Project coordination, management, training, dissemination, and RRI activities
• WP2: Nanoparticle optimization, biodistribution, pharmacokinetics, and GMP process development
• WP3: In vitro and ex vivo functional studies using patient-derived cells and tumor explants
• WP4: In vivo validation in cancer and transplantation mouse models
• WP5: Transcriptomic and epigenetic profiling to identify molecular mechanisms

Expected Impact

SAIL addresses major unmet medical needs in oncology and transplantation medicine. By developing a safe, targeted nanomedicine platform, the project aims to:

• Improve cancer immunotherapy outcomes by overcoming myeloid-mediated immune suppression
• Prolong transplanted organ survival by preventing chronic rejection
• Reduce healthcare burden associated with cancer progression and organ transplant failure
• Create a translational pathway from preclinical research to Phase I clinical trials within 3-4 years post-project
• Foster European competitiveness in nanomedicine and advanced therapy development

Keywords

Nanoparticles, microRNAs, myeloid cells, immune suppression, cancer, transplantation, therapy, PLGA, immunomodulation, nanomedicine

Results

• Reporting and Dissemination – Phase 1 (2025)