Targeting tertiary lymphoid structures using magneto-margination

Introduction

Tertiary lymphoid structures (TLS) are ectopic lymphoid tissues that drive immune responses at sites of chronic inflammation. They are of widespread interest in biology and medicine since their presence dramatically influences disease course in autoimmune disorders, infection, and cancer.

Challenges in Detection

However, due to their small size and their development in chronically altered tissues, TLS cannot be selectively targeted or detected by imaging.

Project Objectives

The current project aims at developing new methods to map and eventually destroy the TLS in a non-invasive manner.

Methodology

To this aim, a new formulation of injectable superparamagnetic particles will be produced and targeted to the TLS. A set of innovations in contrast agent design and material chemistry will be developed to dramatically increase targeting efficiency compared to existing methods.

Innovations and Technologies

By combining these innovations, intravenously injected superparamagnetic particles will accumulate in TLS in large numbers. This accumulation will allow their non-invasive detection by:

1. Clinically available imaging modalities (magnetic resonance imaging)
2. Emerging technologies (magnetic particle imaging)

Potential Applications

This will also open the possibility of thermal destruction of TLS using magnetic hyperthermia, providing a way to suppress a local immune response without affecting systemic immunity.

Clinical Relevance

The scientific advances and technologies of the MAGMA project will have clinically relevant applications, such as:

• Diagnosis of chronic inflammation
• Selection of patients for treatment with immune checkpoint inhibitors in cancer
• Spatially selective suppression of immunity in autoimmune diseases