Targeted Repolarization of Tumor-Associated Macrophages via Imidazoquinoline-Linked Nanobodies.
Targeted Repolarization of Tumor-Associated Macrophages via Imidazoquinoline-Linked Nanobodies.
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DOI：
10.1002/advs.202004574
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发表时间：
2021-05
期刊：
影响因子：
--
通讯作者：
Nuhn L
中科院分区：
文献类型：
--
作者：
Bolli E;Scherger M;Arnouk SM;Pombo Antunes AR;Straßburger D;Urschbach M;Stickdorn J;De Vlaminck K;Movahedi K;Räder HJ;Hernot S;Besenius P;Van Ginderachter JA;Nuhn L
肿瘤相关巨噬细胞（tam）促进肿瘤内的免疫抑制微环境，因此被认为是下一代癌症免疫治疗的有希望的靶点。为了将其表型再极化为肿瘤杀伤状态，Toll样受体7/8激动剂咪唑喹啉IMDQ被位点特异性和定量地偶联到单链抗体片段，即所谓的纳米体，靶向tam上的巨噬细胞甘露糖受体（MMR）。静脉注射这些偶联物导致肿瘤和细胞特异性的IMDQ递送到mmr高的tam中，导致肿瘤生长显著下降。这伴随着tam向促炎表型的再极化和抗肿瘤T细胞反应的增加。因此，这种纳米体-药物偶联物的治疗益处可能为有效的巨噬细胞再教育癌症免疫疗法铺平道路。咪唑喹啉类药物作为toll样受体7/8激动剂可以通过靶向纳米体的巨噬细胞甘露糖受体在肿瘤微环境中细胞特异性地递送至肿瘤前巨噬细胞。观察到它们的表型再极化进入促炎症状态，从而显著降低肿瘤生长。这种咪唑喹啉连接的纳米体药物偶联物可以被认为是有前途的巨噬细胞再教育癌症免疫疗法。
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. 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.
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影响因子：
4.6
作者：
Krüwel T;Nevoltris D;Bode J;Dullin C;Baty D;Chames P;Alves F
通讯作者：
Alves F
影响因子：
14
作者：
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影响因子：
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作者：
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通讯作者：
Dowling, David J
影响因子：
4.7
作者：
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通讯作者：
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影响因子：
11.2
作者：
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通讯作者：
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