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

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.
Original languageEnglish
Article numbere202207508
Number of pages7
JournalAngewandte Chemie International Edition
Issue number41
Publication statusPublished - 22 Aug 2022

Keywords / Materials (for Non-textual outputs)

  • CCL2
  • cancer
  • cathepsins
  • probes
  • prodrugs


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