Targeted Repolarization of Tumor‐Associated Macrophages via Imidazoquinoline‐Linked Nanobodies. Issue 10 (8th March 2021)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Advanced science. Volume 8:Issue 10(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-03-08
• Subjects: cancer immunotherapy -- drug delivery -- M2 macrophages -- nanobodies -- repolarization -- TLR 7/8 agonist -- tumor associated macrophages; Science -- Periodicals; 505
• DOI: 10.1002/advs.202004574
• Languages: English
• ISSNs: 2198-3844

Abstract

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. Abstract : Imidazoquinolines as toll‐like receptor 7/8 agonists can cell‐specifically be delivered via a macrophage mannose receptor targeting nanobodies to pro‐tumoral macrophages in the tumor microenvironment. A repolarization of their phenotype into a pro‐inflammatory state is observed affording significant decline in tumor growth. Such imidazoquinoline‐linked nanobody‐drug conjugates can be considered as promising macrophage re‐educating cancer immunotherapies.