Enhancing preventive and therapeutic cancer vaccine efficacy through biotherapeutic ligand-associated extracellular vesicles.

Autor: Kahraman T; Department of Molecular Biology and Genetics, Bilkent University, 06800, Bilkent, Ankara, Turkey; Thorvacs Vaccine, Drug, Biologic Products and Biotechnology Research and Development Company, 06800 Ankara, Turkey., Akpinar GG; Department of Molecular Biology and Genetics, Bilkent University, 06800, Bilkent, Ankara, Turkey; Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institute, Karolinska University Hospital, SE-171 64 Stockholm, Sweden., Yildirim M; Department of Molecular Biology and Genetics, Bilkent University, 06800, Bilkent, Ankara, Turkey; Thorlab, Therapeutic Oligonucleotide Research Laboratory, Izmir Biomedicine and Genome Center, Izmir, Turkey., Larssen P; Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institute, Karolinska University Hospital, SE-171 64 Stockholm, Sweden., Bayyurt-Kocabas B; Department of Molecular Biology and Genetics, Bilkent University, 06800, Bilkent, Ankara, Turkey; Dept of Biological Sciences, METU, 06800 Ankara, Turkey., Yagci FC; Department of Molecular Biology and Genetics, Bilkent University, 06800, Bilkent, Ankara, Turkey; Thorvacs Vaccine, Drug, Biologic Products and Biotechnology Research and Development Company, 06800 Ankara, Turkey., Gursel A; Department of Molecular Biology and Genetics, Bilkent University, 06800, Bilkent, Ankara, Turkey., Horuluoglu BH; Department of Molecular Biology and Genetics, Bilkent University, 06800, Bilkent, Ankara, Turkey., Yazar V; Department of Molecular Biology and Genetics, Bilkent University, 06800, Bilkent, Ankara, Turkey., Ayanoglu IC; Dept of Biological Sciences, METU, 06800 Ankara, Turkey., Yildirim TC; Department of Molecular Biology and Genetics, Bilkent University, 06800, Bilkent, Ankara, Turkey; Thorlab, Therapeutic Oligonucleotide Research Laboratory, Izmir Biomedicine and Genome Center, Izmir, Turkey., Evcili I; Department of Molecular Biology and Genetics, Bilkent University, 06800, Bilkent, Ankara, Turkey; Thorlab, Therapeutic Oligonucleotide Research Laboratory, Izmir Biomedicine and Genome Center, Izmir, Turkey., Yilmaz IC; Thorlab, Therapeutic Oligonucleotide Research Laboratory, Izmir Biomedicine and Genome Center, Izmir, Turkey; Dept of Biological Sciences, METU, 06800 Ankara, Turkey., Eldh M; Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institute, Karolinska University Hospital, SE-171 64 Stockholm, Sweden., Gabrielsson S; Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institute, Karolinska University Hospital, SE-171 64 Stockholm, Sweden., Guler U; Department of Chemistry, Hacettepe University, 06800 Ankara, Turkey., Salih B; Department of Chemistry, Hacettepe University, 06800 Ankara, Turkey., Gursel M; Thorlab, Therapeutic Oligonucleotide Research Laboratory, Izmir Biomedicine and Genome Center, Izmir, Turkey; Dept of Biological Sciences, METU, 06800 Ankara, Turkey., Gursel I; Department of Molecular Biology and Genetics, Bilkent University, 06800, Bilkent, Ankara, Turkey; Thorlab, Therapeutic Oligonucleotide Research Laboratory, Izmir Biomedicine and Genome Center, Izmir, Turkey. Electronic address: ihsangursel@ibg.edu.tr.
Jazyk: angličtina
Zdroj: Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2024 Dec; Vol. 376, pp. 618-631. Date of Electronic Publication: 2024 Oct 25.
DOI: 10.1016/j.jconrel.2024.10.025
Abstrakt: Extracellular vesicles (EVs), secreted by almost all living cells, have gained significant attention for their role in intercellular communication and their potential as versatile carriers for biotherapeutics. However, the clinical translation of EV-based therapies faces significant challenges, primarily due to the lack of efficient methods for loading biotherapeutic agents into EVs. This study introduces a simple, reproducible strategy for the simultaneous incorporation of various biotherapeutics within EVs. The process is gentle and preserves the essential physicochemical and biological characteristics of EVs, thereby protecting labile ligands from premature degradation and elimination. The binding and uptake efficiency of EVs by target cells reached approximately 97 % within 24 h of incubation. Administration of EVs loaded with oligodeoxynucleotides (ODN) resulted in a 4-fold increase in IFNγ + CD4 + T cells and a 5-fold increase in IFNγ + CD8 + T cells in the spleens and lymph nodes. Additionally, the co-administration of EVs with ODN and ovalbumin (OVA) induced elevated Th1-biased antibody responses and antigen-specific cytotoxic T-cell responses, providing long-lasting complete protection in 60 % of mice against T-cell thymoma challenge. Furthermore, EVs associated with three different ligands (OVA, CpG-ODN, and α-GalCer) effectively regressed established murine melanoma and significantly improved survival rates in mice. This study presents a powerful and promising approach to overcoming the limitations of EV-based cancer vaccines, advancing the development of effective cancer immunotherapies. SUMMARY: Immunization with EVs that are co-associated with antigen and biotherapeutic cargo through a lyophilization-based technique elicits potent anti-cancer immunity.
Competing Interests: Declaration of competing interest The funding bodies played no role in study design, data collection, decision to publish, or preparation of the manuscript. The authors (I.G. & M.G.) declare that they have the inventor rights on CpG ODN related patents.
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE
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