Floris van Dalen
Tumour-associated macrophages (TAMs) support tumour development and have emerged as regulators of therapeutic response to cytostatic agents and immune checkpoint inhibitors. TAMs display an M2-like phenotype, hallmarked by immunosuppressive factors and increased cysteine cathepsin activity. To target TAMs we have developed a drug delivery approach which induces drug release as it inhibits cysteine cathepsins, so-called inhibitory prodrugs (IPDs). We investigated this IPD approach with a fluorogenic payload to characterise release kinetics, cytostatic drugs to eliminate TAMs and immunomodulatory drugs to modulate the immunosuppressive tumour microenvironment. Lastly, we developed cytokine-mediated and nanoformulated delivery strategies to improve the selective engagement of TAMs.