PEDF-Enriched Extracellular Vesicle for Vessel Normalization to Potentiate Immune Checkpoint Blockade Therapy.

Autor:	Shin S; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06355, Republic of Korea.; School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea., Kim CH; School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea., Son S; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06355, Republic of Korea.; School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea., Lee JA; School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea., Kwon S; School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea., You DG; Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Lee J; School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea., Kim J; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06355, Republic of Korea., Jo DG; Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Republic of Korea.; School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.; ExoStemTech Inc., 55 Hanyangdaehak-ro, Sangnok-gu, Ansan 15588, Republic of Korea., Ko H; School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.; Bionanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea., Park JH; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06355, Republic of Korea.; School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.; Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Republic of Korea.; ExoStemTech Inc., 55 Hanyangdaehak-ro, Sangnok-gu, Ansan 15588, Republic of Korea.
Jazyk:	angličtina
Zdroj:	Biomaterials research [Biomater Res] 2024 Oct 01; Vol. 28, pp. 0068. Date of Electronic Publication: 2024 Oct 01 (Print Publication: 2024).
DOI:	10.34133/bmr.0068
Abstrakt:	The abnormal tumor vasculature acts as the physical and functional barrier to the infiltration and activity of effector T cells, leading to the low response rate of immune checkpoint inhibitors (ICIs). Herein, antiangiogenic extracellular vesicles that enable normalization of the tumor-associated vasculature were prepared to potentiate the efficacy of ICIs. Small extracellular vesicles were exploited as the delivery platform to protect the antiangiogenic protein, pigment epithelium-derived factor (PEDF), from proteolytic degradation. Along with the physicochemical characteristics of the PEDF-enriched extracellular vesicles (P-EVs), their inhibitory effects on migration, proliferation, and tube formation of endothelial cells were investigated in vitro. In tumor-bearing mice, it was confirmed that, compared to bare PEDFs, P-EVs efficiently reduced vessel leakiness, improved blood perfusion, and attenuated hypoxia. Consequently, when combined with anti-PD-1 antibodies, P-EVs remarkably augmented the antitumor immunity, as evidenced by increased infiltration of CD8 + T cells and reduced regulatory T cells. These results suggest that P-EVs are promising therapeutics for tumors refractory to ICIs. Competing Interests: Competing interests: The authors declare the following competing interests: D.-G.J. and J.H.P. are stockholders of ExoStemTech Inc. The other authors declare that they have no competing financial interests. (Copyright © 2024 Sol Shin et al.)
Databáze:	MEDLINE
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