Achieving the golden Grail in solid tumor treatment

Introduction

Macrophage therapy is promising for solid tumor treatment as these cells are continuously recruited into the tumor mass, even in the most hypoxic regions. Our pioneering research demonstrated that macrophages are able to take up ferritins loaded with anti-cancer drugs, creating Macrophage-Drug Conjugates (MDCs), and transfer these to cancer cells to kill them, a phenomenon we named TRAIN.

Project Overview

In my ongoing ERC Starting Grant PROJECT ‘McHAP’, we have proven that MDCs can be successfully used not only to treat solid tumors but also to induce subsequent resistance to tumor re-challenge. Acquisition of resistance to tumor development after specific therapy is a 'Golden Grail' in oncology.

Objectives

Now we aim to turn the MDC technology into a commercial and social value proposition by:

1. Confirming mechanisms of tumor-resistance in tumor-bearing mice.
2. Identifying immune responses.

This is crucial to raise the interest of and establish a co-development (or licensing) deal with big pharma to realize commercialization and clinical uptake of our IP-protected MDC technology.

Methodology

During the ERC PoC project, we will perform:

• High-dimensional spectral flow cytometry.
• Spatial transcriptomics.
• Single-cell transcriptomics of the tumor before and after MDC treatment.

These methods will help us identify mechanisms of tumor-resistance and optimize our business case.

Expected Outcomes

This project will thus provide proof of concept for the immune activation after the MDC treatment and establish the viability, feasibility, commercialization, and overall direction for our innovative MDC technology. This project will substantially contribute to bringing our MDC technology to the market and clinical practice.