Harnessing macrophage-drug conjugates for allogeneic cell-based therapy of solid tumors via the TRAIN mechanism
Abstract
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.
Article Details
Authors (34)
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 Woźniak
Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warszawa, Poland
Giacomo Parisi
Roberta Piacentini
Luca Cassetta
Lesley M. Forrester
Lubomir Bodnar
Tobias Weiss
Alberto Boffi
Paulina Kucharzewska
Tomasz P. Rygiel
Magdalena Krol