AGAINST · Achieving the golden Grail in solid tumor treatment

Macrophage therapy is promising for solid tumor treatment as these cells are continuously recruited into the tumor mass, even 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 and kill them, a phenomenon we named TRAIN. In my ongoing ERC Starting Grant PROJECT McHAP, we have proven that MDCs can be sucessfully used not only to treat solid tumors but also to induce subsequent resistance to the tumor re-challenge. Acquisition of resistance to tumor development after specific therapy is a 'Golden Grail' in oncology.Now we aim to turn the MDC technology into a commercial and social value proposition by confirming mechanisms of tumor-resistance in tumor-bearing mice and identify immune response. This is crucial to raise interest of and establish a co-development (or licensing) deal with big pharmas to realize commercialization and clinical uptake of our IP-protected MDC technology. During the ERC PoC project, we will perform high-dimensional spectral flow cytometry, spatial transcriptomics and single-cell transcriptomics of the tumor before and after MDC treatment to identify mechanisms of tumor-resistance and optimize our business case. This project will thus provide proof of concept for the immune activation after the MDC treatment and thus establish the viability, feasibility, commercialization and overall direction for our innovative MDC technology. This project will substantially contribute to bring our MDC technology to the market and clinical practice.