| Title: |
Harnessing macrophage-drug conjugates for allogeneic cell-based therapy of solid tumors via the TRAIN mechanism |
| Authors: |
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; 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 |
| Publication Year: |
2025 |
| Collection: |
FU Berlin: Refubium |
| Subject Terms: |
Cancer immunotherapy; Drug development; Monocytes and macrophages; Protein translocation; ddc:615 |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
30 Seiten; application/pdf |
| Language: |
English |
| DOI: |
10.17169/refubium-46360 |
| DOI: |
10.1038/s41467-025-56637-9 |
| Availability: |
https://refubium.fu-berlin.de/handle/fub188/46646; https://doi.org/10.17169/refubium-46360; https://doi.org/10.1038/s41467-025-56637-9 |
| Rights: |
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. ; https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.20484C7B |
| Database: |
BASE |