Publikationsdatenbank

Harnessing macrophage-drug conjugates for allogeneic cell-based therapy of solid tumors via the TRAIN mechanism (2025)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Taciak, Bartlomiej

Bialasek, Maciej

Kubiak, Malgorzata

Marszalek, Ilona

Gorczak, Malgorzata

Osadchuk, Olha

Kurpiel, Daria

Strzemecki, Damian

Barwik, Karolina

Skorzynski, Marcin

Nowakowska, Julia

Lipiński, Waldemar

Kiraga, Łukasz

Brancewicz, Jan

Klopfleisch, Robert (WE 12)

Krzemiński, Łukasz

Gorka, Emilia

Smolarska, Anna

Padzinska-Pruszynska, Irena

Siemińska, Małgorzata

Guzek, Jakub

Kutner, Jan

Kisiala, Marlena

Wozniak, Krzysztof

Parisi, Giacomo

Piacentini, Roberta

Cassetta, Luca

Forrester, Lesley M.

Bodnar, Lubomir

Weiss, Tobias

Boffi, Alberto

Kucharzewska, Paulina

Rygiel, Tomasz P.

Krol, Magdalena

Quelle

Nature Communications

Bandzählung: 16

Seiten: 1327

ISSN: 2041-1723

Sprache

Englisch

Verweise

URL (Volltext): https://www.nature.com/articles/s41467-025-56637-9

DOI: 10.1038/s41467-025-56637-9

Pubmed: 39900573

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Treatment of solid tumors remains challenging and therapeutic strategies require continuous development. Tumor-infiltrating macrophages play a pivotal role in tumor dynamics. Here, we present a Macrophage-Drug Conjugate (MDC) platform technology that enables loading macrophages with ferritin-drug complexes. We first show that macrophages actively take up human heavy chain ferritin (HFt) in vitro via macrophage scavenger receptor 1 (MSR1). We further manifest that drug-loaded macrophages transfer ferritin to adjacent cancer cells through a process termed ‘TRAnsfer of Iron-binding protein’ (TRAIN). The TRAIN process requires direct cell-to-cell contact and an immune synapse-like structure. At last, MDCs with various anti-cancer drugs are formulated with their safety and anti-tumor efficacy validated in multiple syngeneic mice and orthotopic human tumor models via different routes of administration. Importantly, MDCs can be prepared in advance and used as thawed products, supporting their clinical applicability. This MDC approach thus represents a promising advancement in the therapeutic landscape for solid tumors.