Harnessing macrophage-drug conjugates for allogeneic cell-based therapy of solid tumors via the TRAIN mechanism
Abstract 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 ferriti...
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2025-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56637-9 |
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| author | Bartlomiej Taciak Maciej Bialasek Malgorzata Kubiak Ilona Marszalek Malgorzata Gorczak Olha Osadchuk Daria Kurpiel Damian Strzemecki Karolina Barwik Marcin Skorzynski Julia Nowakowska Waldemar Lipiński Łukasz Kiraga Jan Brancewicz Robert Klopfleisch Łukasz Krzemiński Emilia Gorka Anna Smolarska Irena Padzinska-Pruszynska Małgorzata Siemińska Jakub Guzek Jan Kutner Marlena Kisiala Krzysztof Wozniak Giacomo Parisi Roberta Piacentini Luca Cassetta Lesley M. Forrester Lubomir Bodnar Tobias Weiss Alberto Boffi Paulina Kucharzewska Tomasz P. Rygiel Magdalena Krol |
| author_facet | Bartlomiej Taciak Maciej Bialasek Malgorzata Kubiak Ilona Marszalek Malgorzata Gorczak Olha Osadchuk Daria Kurpiel Damian Strzemecki Karolina Barwik Marcin Skorzynski Julia Nowakowska Waldemar Lipiński Łukasz Kiraga Jan Brancewicz Robert Klopfleisch Łukasz Krzemiński Emilia Gorka Anna Smolarska Irena Padzinska-Pruszynska Małgorzata Siemińska Jakub Guzek Jan Kutner Marlena Kisiala Krzysztof Wozniak Giacomo Parisi Roberta Piacentini Luca Cassetta Lesley M. Forrester Lubomir Bodnar Tobias Weiss Alberto Boffi Paulina Kucharzewska Tomasz P. Rygiel Magdalena Krol |
| author_sort | Bartlomiej Taciak |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-83a00daf9f684896b6cb93db039be5d4 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-83a00daf9f684896b6cb93db039be5d42025-02-09T12:44:52ZengNature PortfolioNature Communications2041-17232025-02-0116113010.1038/s41467-025-56637-9Harnessing macrophage-drug conjugates for allogeneic cell-based therapy of solid tumors via the TRAIN mechanismBartlomiej Taciak0Maciej Bialasek1Malgorzata Kubiak2Ilona Marszalek3Malgorzata Gorczak4Olha Osadchuk5Daria Kurpiel6Damian Strzemecki7Karolina Barwik8Marcin Skorzynski9Julia Nowakowska10Waldemar Lipiński11Łukasz Kiraga12Jan Brancewicz13Robert Klopfleisch14Łukasz Krzemiński15Emilia Gorka16Anna Smolarska17Irena Padzinska-Pruszynska18Małgorzata Siemińska19Jakub Guzek20Jan Kutner21Marlena Kisiala22Krzysztof Wozniak23Giacomo Parisi24Roberta Piacentini25Luca Cassetta26Lesley M. Forrester27Lubomir Bodnar28Tobias Weiss29Alberto Boffi30Paulina Kucharzewska31Tomasz P. Rygiel32Magdalena Krol33Cellis AGCellis AGCellis AGCellis AGCellis AGCellis AGCellis AGCellis AGCellis AGDepartment of Immunology, Mossakowski Medical Research Institute, Polish Academy of SciencesCellis AGCellis AGCellis AGCellis AGInstitute of Veterinary Pathology, Free University of BerlinBiosens Labs Sp. z o.oCellis AGCenter of Cellular Immunotherapies, Warsaw University of Life SciencesCenter of Cellular Immunotherapies, Warsaw University of Life SciencesCellis AGCenter of Cellular Immunotherapies, Warsaw University of Life SciencesThe International Institute of Molecular Mechanisms and Machines, Polish Academy of SciencesDepartment of Chemistry, Biological and Chemical Research Centre, University of WarsawDepartment of Chemistry, Biological and Chemical Research Centre, University of WarsawDepartment of Biochemical Sciences “Alessandro Rossi Fanelli”, Sapienza University of RomeDepartment of Biochemical Sciences “Alessandro Rossi Fanelli”, Sapienza University of RomeMRC Centre for Reproductive Health, Queen Medical Research Institute, University of EdinburghCentre for Regenerative Medicine, University of EdinburghCellis AGDepartment of Neurology, Clinical Neuroscience Center, University Hospital and University of ZurichCellis AGCellis AGCellis AGCellis AGAbstract 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.https://doi.org/10.1038/s41467-025-56637-9 |
| spellingShingle | Bartlomiej Taciak Maciej Bialasek Malgorzata Kubiak Ilona Marszalek Malgorzata Gorczak Olha Osadchuk Daria Kurpiel Damian Strzemecki Karolina Barwik Marcin Skorzynski Julia Nowakowska Waldemar Lipiński Łukasz Kiraga Jan Brancewicz Robert Klopfleisch Łukasz Krzemiński Emilia Gorka Anna Smolarska Irena Padzinska-Pruszynska Małgorzata Siemińska Jakub Guzek Jan Kutner Marlena Kisiala Krzysztof Wozniak Giacomo Parisi Roberta Piacentini Luca Cassetta Lesley M. Forrester Lubomir Bodnar Tobias Weiss Alberto Boffi Paulina Kucharzewska Tomasz P. Rygiel Magdalena Krol Harnessing macrophage-drug conjugates for allogeneic cell-based therapy of solid tumors via the TRAIN mechanism Nature Communications |
| title | Harnessing macrophage-drug conjugates for allogeneic cell-based therapy of solid tumors via the TRAIN mechanism |
| title_full | Harnessing macrophage-drug conjugates for allogeneic cell-based therapy of solid tumors via the TRAIN mechanism |
| title_fullStr | Harnessing macrophage-drug conjugates for allogeneic cell-based therapy of solid tumors via the TRAIN mechanism |
| title_full_unstemmed | Harnessing macrophage-drug conjugates for allogeneic cell-based therapy of solid tumors via the TRAIN mechanism |
| title_short | Harnessing macrophage-drug conjugates for allogeneic cell-based therapy of solid tumors via the TRAIN mechanism |
| title_sort | harnessing macrophage drug conjugates for allogeneic cell based therapy of solid tumors via the train mechanism |
| url | https://doi.org/10.1038/s41467-025-56637-9 |
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