Open AccessTargeted Repolarization of Tumor‐Associated Macrophages via Imidazoquinoline‐Linked Nanobodies
Author(s) -
Bolli Evangelia,
Scherger Maximilian,
Arnouk Sana M.,
Pombo Antunes Ana Rita,
Straßburger David,
Urschbach Moritz,
Stickdorn Judith,
De Vlaminck Karen,
Movahedi Kiavash,
Räder Hans Joachim,
Hernot Sophie,
Besenius Pol,
Van Ginderachter Jo A.,
Nuhn Lutz
Publication year - 2021
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.202004574
Subject(s) - tumor microenvironment , cancer research , immune system , macrophage , cancer , immunotherapy , medicine , immunology , chemistry , in vitro , biochemistry
Abstract Tumor‐associated macrophages (TAMs) promote the immune suppressive microenvironment inside tumors and are, therefore, considered as a promising target for the next generation of cancer immunotherapies. To repolarize their phenotype into a tumoricidal state, the Toll‐like receptor 7/8 agonist imidazoquinoline IMDQ is site‐specifically and quantitatively coupled to single chain antibody fragments, so‐called nanobodies, targeting the macrophage mannose receptor (MMR) on TAMs. Intravenous injection of these conjugates result in a tumor‐ and cell‐specific delivery of IMDQ into MMR high TAMs, causing a significant decline in tumor growth. This is accompanied by a repolarization of TAMs towards a pro‐inflammatory phenotype and an increase in anti‐tumor T cell responses. Therefore, the therapeutic benefit of such nanobody‐drug conjugates may pave the road towards effective macrophage re‐educating cancer immunotherapies.