Nanobody-Based Targeting of the Macrophage Mannose Receptor for Effective<i>In Vivo</i>Imaging of Tumor-Associated Macrophages

Movahedi, Kiavash; Schoonooghe, Steve; Laoui, Damya; Houbracken, Isabelle; Waelput, Wim; Breckpot, Karine; Bouwens, Luc; Lahoutte, Tony; Baetseĺier, Patrick De; Raes, Geert; Devoogdt, Nick; Ginderachter, Jo A. Van

doi:10.1158/0008-5472.can-11-2994

Cited by 264 publications

(270 citation statements)

References 47 publications

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“…In addition, Movahedi and colleagues generated singledomain antibodies (sdAb) that are specific for the macrophage mannose receptor (MMR or CD206), which they found to be highly expressed on certain TAM subpopulations [56]. The MMR-specific sdAb were able to bind TAMs isolated from multiple tumor types ex vivo as well as in vivo following intravenous injection of sdAb [93]. These pre-clinical results suggest that antigen-specific targeting of TAMs is possible, although it remains to be seen if this will translate to effective therapy.…”

Section: Antigen-specific Targeting Of Tumor-associated Macrophagesmentioning

confidence: 99%

Monocytes and Macrophages in Cancer: Development and Functions

Richards

Hettinger

Feuerer

2012

Cancer Microenvironment

166

122

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Monocytes and tumor-associated macrophages are part of the myeloid family, a group of hematopoietic derived cells. Monocytes are direct precursors of hematopoietic stem cell-derived macrophages. After their recruitment into the tumor tissue, they can differentiate into tumor-associated macrophages, a very heterogeneous cell population in terms of phenotype and pro-tumor function, supporting tumor initiation, local progression and distant metastasis. Therefore, targeting monocytes and macrophages is a promising immunotherapeutic approach. This review will focus on the development of monocytes as macrophage precursors, the functions of tumorassociated macrophages and the possibility of interfering with tumor development and progression by targeting these myeloid cells.

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Section: Antigen-specific Targeting Of Tumor-associated Macrophagesmentioning

confidence: 99%

Monocytes and Macrophages in Cancer: Development and Functions

Richards

Hettinger

Feuerer

2012

Cancer Microenvironment

166

122

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“…3 Mannose receptors are also expressed on a macrophage subset that is found in solid tumors, termed tumor associated macrophages (TAMs) that exert a pro-tumoral function and thus are a target for eradication or reprogramming. 4 Moreover, the C-type lectin DC-SIGN (also termed CD209)…”

Section: Introductionmentioning

confidence: 99%

pH-Degradable Mannosylated Nanogels for Dendritic Cell Targeting

Coen¹,

Vanparijs

Risseeuw³

et al. 2016

Biomacromolecules

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We report on the design of glycosylated nanogels via core-cross-linking of amphiphilic non-watersoluble block copolymers composed of an acetylated glycosylated block and a pentafluorophenyl (PFP) activated ester block prepared by RAFT polymerization. Self-assembly, pH-sensitive corecross-linking and removal of remaining PFP esters and protecting groups is achieved in one-pot yielding fully hydrated sub-100 nm nanogels. Using cell subsets that exhibit high and low expression of the mannose receptor under conditions that suppress active endocytosis, we show that mannosylated but not galactosylated nanogels can efficiently target the mannose receptor (MR) that is expressed on the cell surface of primary dendritic cells (DCs). These nanogels hold promise for immunological applications involving DCs and macrophage subsets.

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“…The potential of radiolabeled camelid single-domain antibody fragments (sdAbs; VHH, Nanobodies [Nanobody is a trade name of Ablynx NV]) for imaging of macrophages and dendritic cells has been demonstrated (7)(8)(9). 99m Tc-labeled sdAbs specifically targeting murine MMR were found to be interesting new probes for preclinical imaging of MHC II low TAMs within the tumor microenvironment (10).…”

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confidence: 99%

PET Imaging of Macrophage Mannose Receptor–Expressing Macrophages in Tumor Stroma Using ¹⁸F-Radiolabeled Camelid Single-Domain Antibody Fragments

et al. 2015

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Tumor-associated macrophages constitute a major component of the stroma of solid tumors, encompassing distinct subpopulations with different characteristics and functions. We aimed to identify M2-oriented tumor-supporting macrophages within the tumor microenvironment as indicators of cancer progression and prognosis, using PET imaging. This can be realized by designing 18 F-labeled camelid single-domain antibody fragments (sdAbs) specifically targeting the macrophage mannose receptor (MMR), which has been identified as an important biomarker on this cell population. Methods: Crossreactive anti-MMR sdAbs were generated after immunization of an alpaca with the extracellular domains of both human and mouse MMR. The lead binder was chosen on the basis of comparisons of binding affinity and in vivo pharmacokinetics. The PET tracer 18 F-fluorobenzoate (FB)-anti-MMR sdAb was developed using the prosthetic group N-succinimidyl-4-18 F-fluorobenzoate ( 18 F-SFB), and its biodistribution, tumor-targeting potential, and specificity in terms of macrophage and MMR targeting were evaluated in mouse tumor models. Results: Four sdAbs were selected after affinity screening, but only 2 were found to be cross-reactive for human and mouse MMR. The lead anti-MMR 3.49 sdAb, bearing an affinity of 12 and 1.8 nM for mouse and human MMR, respectively, was chosen for its favorable in vivo biodistribution profile and tumor-targeting capacity. 18 F-FB-anti-MMR 3.49 sdAb was synthesized with a 5%-10% radiochemical yield using an automated and optimized protocol. In vivo biodistribution analyses showed fast clearance via the kidneys and retention in MMRexpressing organs and tumor. The kidney retention of the fluorinated sdAb was 20-fold lower than a 99m Tc-labeled counterpart. Compared with MMR-and C-C chemokine receptor 2-deficient mice, significantly higher uptake was observed in tumors grown in wild-type mice, demonstrating the specificity of the 18 F tracer for MMR and macrophages, respectively. Conclusion: Anti-MMR 3.49 was denoted as the lead cross-reactive MMR-targeting sdAb. 18 F radiosynthesis was optimized, providing an optimal probe for PET imaging of the tumor-promoting macrophage subpopulation in the tumor stroma. Dur ing tumor development, myeloid cells are attracted to the tumor stroma. These infiltrating immune cells are versatile, adopting different activation states in response to a changing microenvironment, leading to subsets of tumor-associated macrophages (TAMs) with specialized functions (1,2). Two main morphologically distinct TAM subsets can be distinguished on the basis of major histocompatibility complex (MHC) class II expression levels in multiple mouse tumor models. Tumor promotion has been linked with an accumulation of M2-oriented MHC II low TAMs in lung and breast carcinoma (3,4). Accordingly, MHC II low TAMs were found to reside primarily in less oxygenated zones, express hypoxia-regulated genes, and facilitate the angiogenic switch (5). Interestingly, the macrophage mannose receptor (MMR, CD206), a typical M2...

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Nanobody-Based Targeting of the Macrophage Mannose Receptor for EffectiveIn VivoImaging of Tumor-Associated Macrophages

Abstract: Tumor-associated macrophages (TAM) are an important component of the tumor stroma and exert several tumor-promoting activities. Strongly pro-angiogenic TAMs that reside in hypoxic tumor areas highly express macrophage mannose receptor (MMR, CD206)

Cited by 264 publications

References 47 publications

Monocytes and Macrophages in Cancer: Development and Functions

Monocytes and Macrophages in Cancer: Development and Functions

pH-Degradable Mannosylated Nanogels for Dendritic Cell Targeting

PET Imaging of Macrophage Mannose Receptor–Expressing Macrophages in Tumor Stroma Using ¹⁸F-Radiolabeled Camelid Single-Domain Antibody Fragments

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Nanobody-Based Targeting of the Macrophage Mannose Receptor for EffectiveIn VivoImaging of Tumor-Associated Macrophages

Abstract: Tumor-associated macrophages (TAM) are an important component of the tumor stroma and exert several tumor-promoting activities. Strongly pro-angiogenic TAMs that reside in hypoxic tumor areas highly express macrophage mannose receptor (MMR, CD206)

Cited by 264 publications

References 47 publications

Monocytes and Macrophages in Cancer: Development and Functions

Monocytes and Macrophages in Cancer: Development and Functions

pH-Degradable Mannosylated Nanogels for Dendritic Cell Targeting

PET Imaging of Macrophage Mannose Receptor–Expressing Macrophages in Tumor Stroma Using 18F-Radiolabeled Camelid Single-Domain Antibody Fragments

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Product

Resources

About

PET Imaging of Macrophage Mannose Receptor–Expressing Macrophages in Tumor Stroma Using ¹⁸F-Radiolabeled Camelid Single-Domain Antibody Fragments