Antibody-displaying extracellular vesicles for targeted cancer therapy.

Journal

Nature biomedical engineering
ISSN: 2157-846X
Titre abrégé: Nat Biomed Eng
Pays: England
ID NLM: 101696896

Informations de publication

Date de publication:
20 May 2024
Historique:
received: 20 03 2023
accepted: 08 04 2024
medline: 21 5 2024
pubmed: 21 5 2024
entrez: 20 5 2024
Statut: aheadofprint

Résumé

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.

Identifiants

DOI: 10.1038/s41551-024-01214-6 PMID: 38769158
pubmed: 38769158
doi: 10.1038/s41551-024-01214-6
pii: 10.1038/s41551-024-01214-6
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Vetenskapsrådet (Swedish Research Council)
ID : 2022-02449
Organisme : Vetenskapsrådet (Swedish Research Council)
ID : 2021-02407
Organisme : Vetenskapsrådet (Swedish Research Council)
ID : 4-258/2021
Organisme : Stiftelsen för Strategisk Forskning (Swedish Foundation for Strategic Research)
ID : SM19-0007

Informations de copyright

© 2024. The Author(s).

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Auteurs

Oscar P B Wiklander (OPB)

Department of Laboratory Medicine, Unit for Biomolecular and Cellular Medicine, Karolinska Institutet, Stockholm, Sweden. oscar.wiklander@ki.se.
Breast Center, Karolinska Comprehensive Cancer Center, Karolinska University Hospital, Stockholm, Sweden. oscar.wiklander@ki.se.
Karolinska ATMP Center, ANA Futura, Huddinge, Sweden. oscar.wiklander@ki.se.
ORCID: 0000-0003-1176-8114

Doste R Mamand (DR)

Department of Laboratory Medicine, Unit for Biomolecular and Cellular Medicine, Karolinska Institutet, Stockholm, Sweden.
Breast Center, Karolinska Comprehensive Cancer Center, Karolinska University Hospital, Stockholm, Sweden.
Karolinska ATMP Center, ANA Futura, Huddinge, Sweden.

Dara K Mohammad (DK)

Department of Medicine Huddinge, Karolinska Institute, Stockholm, Sweden.
College of Agricultural Engineering Sciences, Salahaddin University-Erbil, Erbil, Iraq.
ORCID: 0000-0001-9201-0991

Wenyi Zheng (W)

Department of Laboratory Medicine, Unit for Biomolecular and Cellular Medicine, Karolinska Institutet, Stockholm, Sweden.
Karolinska ATMP Center, ANA Futura, Huddinge, Sweden.
Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Huddinge, Sweden.
ORCID: 0000-0003-2416-5822

Rim Jawad Wiklander (R)

Department of Laboratory Medicine, Unit for Biomolecular and Cellular Medicine, Karolinska Institutet, Stockholm, Sweden.
Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Huddinge, Sweden.

Taras Sych (T)

Science for Life Laboratory, Department of Women's and Children's Health, Karolinska Institutet, Solna, Sweden.

Antje M Zickler (AM)

Department of Laboratory Medicine, Unit for Biomolecular and Cellular Medicine, Karolinska Institutet, Stockholm, Sweden.
Karolinska ATMP Center, ANA Futura, Huddinge, Sweden.
Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Huddinge, Sweden.
ORCID: 0000-0001-5001-6586

Xiuming Liang (X)

Department of Laboratory Medicine, Unit for Biomolecular and Cellular Medicine, Karolinska Institutet, Stockholm, Sweden.
Karolinska ATMP Center, ANA Futura, Huddinge, Sweden.
Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Huddinge, Sweden.

Heena Sharma (H)

Evox Therapeutics Limited, Oxford, UK.

Andrea Lavado (A)

Evox Therapeutics Limited, Oxford, UK.

Jeremy Bost (J)

Department of Laboratory Medicine, Unit for Biomolecular and Cellular Medicine, Karolinska Institutet, Stockholm, Sweden.
Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Huddinge, Sweden.

Samantha Roudi (S)

Department of Laboratory Medicine, Unit for Biomolecular and Cellular Medicine, Karolinska Institutet, Stockholm, Sweden.
Karolinska ATMP Center, ANA Futura, Huddinge, Sweden.
Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Huddinge, Sweden.

Giulia Corso (G)

Department of Laboratory Medicine, Unit for Biomolecular and Cellular Medicine, Karolinska Institutet, Stockholm, Sweden.
Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Huddinge, Sweden.
ORCID: 0000-0002-1145-0862

Angus J Lennaárd (AJ)

Department of Laboratory Medicine, Unit for Biomolecular and Cellular Medicine, Karolinska Institutet, Stockholm, Sweden.
Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Huddinge, Sweden.

Manuchehr Abedi-Valugerdi (M)

Department of Laboratory Medicine, Unit for Biomolecular and Cellular Medicine, Karolinska Institutet, Stockholm, Sweden.
Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Huddinge, Sweden.

Imre Mäger (I)

Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
ORCID: 0000-0003-2242-7227

Evren Alici (E)

Department of Medicine Huddinge, Karolinska Institute, Stockholm, Sweden.
Hematology Center, Karolinska University Hospital, Stockholm, Sweden.

Erdinc Sezgin (E)

Science for Life Laboratory, Department of Women's and Children's Health, Karolinska Institutet, Solna, Sweden.
ORCID: 0000-0002-4915-388X

Joel Z Nordin (JZ)

Department of Laboratory Medicine, Unit for Biomolecular and Cellular Medicine, Karolinska Institutet, Stockholm, Sweden.
Karolinska ATMP Center, ANA Futura, Huddinge, Sweden.
Department of Clinical Immunology and Transfusion Medicine (KITM), Karolinska University Hospital, Stockholm, Sweden.
ORCID: 0000-0002-3653-7710

Dhanu Gupta (D)

Department of Laboratory Medicine, Unit for Biomolecular and Cellular Medicine, Karolinska Institutet, Stockholm, Sweden.
Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Huddinge, Sweden.
Department of Paediatrics, University of Oxford, Oxford, UK.

André Görgens (A)

Department of Laboratory Medicine, Unit for Biomolecular and Cellular Medicine, Karolinska Institutet, Stockholm, Sweden.
Karolinska ATMP Center, ANA Futura, Huddinge, Sweden.
Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Huddinge, Sweden.
Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Duisburg, Germany.
ORCID: 0000-0001-9198-0857

Samir El Andaloussi (S)

Department of Laboratory Medicine, Unit for Biomolecular and Cellular Medicine, Karolinska Institutet, Stockholm, Sweden. samir.el-andaloussi@ki.se.
Karolinska ATMP Center, ANA Futura, Huddinge, Sweden. samir.el-andaloussi@ki.se.
Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Huddinge, Sweden. samir.el-andaloussi@ki.se.
ORCID: 0000-0003-4468-9113

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