Enzyme‐Activatable Chemokine Conjugates for In Vivo Targeting of Tumor‐Associated Macrophages
Nicole D. Barth,Floris J. van Dalen,Utsa Karmakar,Marco Bertolini,Lorena Mendive-Tapia,Takanori Kitamura,Martijn Verdoes,Marc Vendrell +7 more
- Vol. 61, Iss: 41
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TLDR
The first enzyme-activatable chemokine conjugates for effective targeting of defined macrophage subsets in live tumors are reported, opening new avenues in the design of targeted theranostic probes for immune cells in the tumor microenvironment.Abstract:
Abstract Increased levels of tumor‐associated macrophages (TAMs) are indicators of poor prognosis in most cancers. Although antibodies and small molecules blocking the recruitment of macrophages to tumors are under evaluation as anticancer therapies, these strategies are not specific for macrophage subpopulations. Herein we report the first enzyme‐activatable chemokine conjugates for effective targeting of defined macrophage subsets in live tumors. Our constructs exploit the high expression of chemokine receptors (e.g., CCR2) and the activity of cysteine cathepsins in TAMs to target these cells selectively over other macrophages and immune cells (e.g., neutrophils, T cells, B cells). Furthermore, we demonstrate that cathepsin‐activatable chemokines are compatible with both fluorescent and therapeutic cargos, opening new avenues in the design of targeted theranostic probes for immune cells in the tumor microenvironment.read more
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Journal ArticleDOI
Enzyme‐Activatable Chemokine Conjugates for In Vivo Targeting of Tumor‐Associated Macrophages
Nicole D. Barth,Floris J. van Dalen,Utsa Karmakar,Marco Bertolini,Lorena Mendive-Tapia,Takanori Kitamura,Martijn Verdoes,Marc Vendrell +7 more
TL;DR: The first enzyme-activatable chemokine conjugates for effective targeting of defined macrophage subsets in live tumors are reported, opening new avenues in the design of targeted theranostic probes for immune cells in the tumor microenvironment.
Journal ArticleDOI
Fluorogenic Granzyme A Substrates Enable Real-Time Imaging of Adaptive Immune Cell Activity.
Zhiming Cheng,Emily J. Thompson,Lorena Mendive-Tapia,Jamie I. Scott,Samuel John Benson,Takanori Kitamura,Ana Senan-Salinas,Youhani H. Samarakoon,Edward W. Roberts,Maykel Arias,Julián Pardo,Eva M. Galvez,Marc Vendrell +12 more
TL;DR: In this article , the authors design near-infrared fluorogenic substrates for human granzyme A (GzmA) and mouse GzmA and demonstrate that the probes can image how adaptive immune cells respond to antigen-driven recognition of cancer cells in real time.
Journal ArticleDOI
Targeting Tumor-Associated Macrophages for Imaging
TL;DR: A review of commonly used nanomaterials for TAM targeting imaging probes, including metal-based nanoprobes (iron, manganese, gold, silver), fluorine-19-based nanrobes, radiolabeled agents, near-infrared fluorescence dyes and ultrasonic nanobubbles, is presented in this article .
Journal ArticleDOI
Targeting TAMs
TL;DR: Enzyme-activatable chemokine probes have been shown to selectively target tumour-associated macrophages for the first time.
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