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RESEARCH PRODUCT
Targeted Repolarization of Tumor‐Associated Macrophages via Imidazoquinoline‐Linked Nanobodies
Sana M. ArnoukSophie HernotMaximilian SchergerEvangelia BolliAna Rita Pombo AntunesHans Joachim RäderJudith StickdornMoritz UrschbachDavid StraßburgerJo A. Van GinderachterKaren De VlaminckPol BeseniusKiavash MovahediLutz Nuhnsubject
Lung NeoplasmsGeneral Chemical Engineeringmedicine.medical_treatmentGeneral Physics and AstronomyMedicine (miscellaneous)TLR 7/8 agonist02 engineering and technology01 natural scienceschemistry.chemical_compoundCancer immunotherapyTumor-Associated MacrophagesTumor MicroenvironmentMacrophageM2 macrophagesGeneral Materials ScienceReceptorResearch ArticlesMice KnockoutMembrane GlycoproteinsChemistrytumor associated macrophagesQGeneral EngineeringImidazoles021001 nanoscience & nanotechnologynanobodiesmedicine.anatomical_structureDrug deliveryQuinolines0210 nano-technologyMannose ReceptorResearch ArticleT cellScience010402 general chemistryBiochemistry Genetics and Molecular Biology (miscellaneous)Immune systemmedicineAnimalsrepolarizationcancer immunotherapyCancerSingle-Domain Antibodiesmedicine.disease0104 chemical sciencesImidazoquinolineMice Inbred C57BLDisease Models AnimalToll-Like Receptor 6Toll-Like Receptor 7drug deliveryCancer researchdescription
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 MMRhigh 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2021-03-08 |