Exciting New Macrophage Cell Therapy Option

New research published in Nature Communications offers an exciting new cell therapy option using allogeneic macrophage drug conjugates (MDC) to better attack solid tumors, in an effort to overcome some of the limitations experienced by other cell-based therapies.  

The work was led by scientists at Cellis AG, a European biotechnology company with focus in cell-based oncology therapy based in Zurich, Warsaw University of Life Sciences and collaborators in Berlin and Edinburgh.

The methodology relies upon a novel mechanism for the preferential in vitro uptake of human heavy chain ferritin (HFt) by human monocyte-derived macrophages (hMDM). This novel clathrin-mediated endocytosis mechanism, in addition to the well-understood transferrin receptor 1 (TfR1/CD71), predominantly utilised a Class A Scavenger Receptor - MSR-1. Both receptors are highly expressed on macrophages. The resulting efficient loading of macrophages was shown not to be cytotoxic to the cells.

Further, central to the therapeutic strategy was the ability to pre-load HFt with small molecule drugs at useful drug/protein ratios. The resulting HFt-drug conjugates were found to be a highly stable resource to load hMDM.

hMDM were found to be the most suitable cell type, importantly of allogeneic origin and which were highly amenable to cryopreservation.

The resulting allogeneic macrophage drug conjugates (MDC) were then tested for their ability to target cancer cells and to determine the mechanism.  MDCs targeted tumor cells and cell killing relied upon Hft-drug conjugate transfer from MDC to tumour cells by direct cell-cell contact by a process termed TRAIN (TRAnsfer of Iron proteiN). A wide range of solid tumour cell lines were tested, with low side-effects, highly targeted to the tumour cells and demonstrating good levels of apoptosis. In a variety of in vivo models, xenograft tumours shrank, cell proliferation was reduced and animals maintained weight.

MDCs were also combined with stand-alone therapeutic agents e.g. checkpoint inhibitors, to significant effect.

DRAQ7™ was used in a variety of assays to determine both unwanted and desired cytotoxicities. DRAQ7™ has ideal properties for development of cell therapies, in cross-platform cell-based assays - time-lapse cell-cell killing assays, product quality assurance analysis and more. It is a chemically-defined reagent manufactured following the ISO 9001:2015 quality system.

Reference:
Taciak B, Bialasek M, Kubiak M, et al. Harnessing macrophage-drug conjugates for allogeneic cell-based therapy of solid tumors via the TRAIN mechanism. Nature Communications ( 2025) 16:1327. https://doi.org/10.1038/s41467-025-56637-9