2024-05-20 カロリンスカ研究所(KI)
<関連情報>
- https://news.ki.se/bodys-message-in-a-bottle-delivers-targeted-cancer-treatment
- https://www.nature.com/articles/s41551-024-01214-6
がん標的治療のための抗体発現細胞外小胞 Antibody-displaying extracellular vesicles for targeted cancer therapy
Oscar P. B. Wiklander,Doste R. Mamand,Dara K. Mohammad,Wenyi Zheng,Rim Jawad Wiklander,Taras Sych,Antje M. Zickler,Xiuming Liang,Heena Sharma,Andrea Lavado,Jeremy Bost,Samantha Roudi,Giulia Corso,Angus J. Lennaárd,Manuchehr Abedi-Valugerdi,Imre Mäger,Evren Alici,Erdinc Sezgin,Joel Z. Nordin,Dhanu Gupta,André Görgens & Samir EL Andaloussi
Nature Biomedical Engineering Published:20 May 2024
DOI:https://doi.org/10.1038/s41551-024-01214-6
Abstract
Extracellular vesicles (EVs) function as natural delivery vectors and mediators of biological signals across tissues. Here, by leveraging these functionalities, we show that EVs decorated with an antibody-binding moiety specific for the fragment crystallizable (Fc) domain can be used as a modular delivery system for targeted cancer therapy. The Fc-EVs can be decorated with different types of immunoglobulin G antibody and thus be targeted to virtually any tissue of interest. Following optimization of the engineered EVs by screening Fc-binding and EV-sorting moieties, we show the targeting of EVs to cancer cells displaying the human epidermal receptor 2 or the programmed-death ligand 1, as well as lower tumour burden and extended survival of mice with subcutaneous melanoma tumours when systemically injected with EVs displaying an antibody for the programmed-death ligand 1 and loaded with the chemotherapeutic doxorubicin. EVs with Fc-binding domains may be adapted to display other Fc-fused proteins, bispecific antibodies and antibody–drug conjugates.
