Single-domain antibody fusion proteins can target and shuttle functional proteins into macrophage mannose receptor expressing macrophages

Journal of Controlled Release : Official Journal of the Controlled Release Society
Yannick De VlaeminckKarine Breckpot

Abstract

The tumor microenvironment of numerous prevalent cancer types is abundantly infiltrated with tumor-associated macrophages (TAMs). Macrophage mannose receptor (MMR or CD206) expressing TAMs have been shown to be key promoters of tumor progression and major opponents of successful cancer therapy. Therefore, depleting MMR+ TAMs is an interesting approach to synergize with current antitumor therapies. We studied the potential of single-domain antibodies (sdAbs) specific for MMR to target proteins to MMR+ TAMs. Anti-MMR sdAbs were genetically coupled to a reporter protein, mWasabi (wasabi green, WG), generating sdAb "drug" fusion proteins (SFPs), referred to as WG-SFPs. The resulting WG-SFPs were highly efficient in targeting MMR+ macrophages both in vitro and in vivo. As we showed that second mitochondria-derived activator of caspase (SMAC) mimetics modulate MMR+ macrophages, we further coupled the anti-MMR sdAb to an active form of SMAC, referred to as tSMAC. The resulting tSMAC-SFPs were able to bind and upregulate caspase3/7 activity in MMR+ macrophages in vitro. In conclusion, we report the proof-of-concept of an elegant approach to conjugate anti-MMR sdAbs to proteins, which opens new avenues for targeted manipulation of MMR+ ...Continue Reading

Citations

Aug 15, 2020·Frontiers in Oncology·Emily Y Yang, Khalid Shah
Feb 11, 2020·Journal of Drug Targeting·Tongtong QiGuimei Lin
Dec 4, 2020·Cancers·Yannick De De VlaeminckJo A Van Ginderachter
Feb 23, 2021·Macromolecular Bioscience·Anton V LopukhovAlexander V Kabanov

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Imaging

Imaging techniques, including CT and MR, have become essential to tumor detection, diagnosis, and monitoring. Here is the latest research on cancer imaging.

Related Papers

Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine
Anneleen BlykersVicky Caveliers
Archives of Disease in Childhood
David Elliman, Helen Bedford
Adverse Drug Reactions and Toxicological Reviews
A P Fletcher
© 2022 Meta ULC. All rights reserved