W162 - Macrophage-Drug Conjugate (MDC): A Promising Paradigm for Cell-Based Immunotherapy for Solid Tumors

Maciej Białasek – Cellis AG; Bartłomiej Taciak – Cellis AG; Miaomiao Sun – University Hospital Zurich; Paulina Kucharzewska-Simebieda – Warsaw University of Life Sciences; Ilona Marszalek – Cellis AG; Małgorzata Górczak – Warsaw University of Life Sciences; Małgorzata Kubiak – Warsaw University of Life Sciences; Daria Kurpiel – Cellis AG; Emilia Gorka – Warsaw University of Life Sciences; Jan Brancewicz – Cellis AG; Konrad Gabrusiewicz – Cellis AG; Lubomir Bodnar – Cellis AG; Tobias Weiss – University Hospital Zurich; Alberto Boffi – Sapienza University of Rome; Tomasz Rygiel – Cellis AG

Abstract Text: Solid tumors remain challenging for therapeutic treatments, requiring the search for innovative treatment strategies. Macrophages known to infiltrate tumors due to signals from cancer cells, play a pivotal role in tumor dynamics. This study presents a method for loading macrophages with ferritin-drug complexes introducing the concept of a Macrophage-Drug Conjugate (MDC). Ferritin's protein-cage structure makes it an efficient drug carrier, while macrophages demonstrate a marked ability to internalize substantial amounts of ferritin. We have discovered a novel process where drug-loaded macrophages transfer ferritin to adjacent cancer cells that we called the "TRAnsfer of Iron-binding protein" (TRAIN). Crucially the TRAIN process requires direct cell-cell contact and the formation of an immune synapse-like structure. Macrophages loaded with ferritin conjugated to the cytotoxic drug exhibited highly potent anti-cancer activity in various orthotopic solid tumor models (glioblastoma, ovarian cancer, pancretic cancer leading to complete tumor elimination) and in patient tumor samples. Next, macrophages phagocyte cancer cells and activate immune system and immune memory leading to anti-tumor resistance. Our work lays the foundation for translating this potent adoptive cell therapy into clinical trials for solid tumor treatment.