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T-Cell-Derived Nanovesicles for Cancer Immunotherapy
Cited 43 time in
Web of Science
Cited 43 time in Scopus
- Authors
- Issue Date
- 2021-08
- Citation
- Advanced Materials, Vol.33 No.33, p. 2101110
- Abstract
- Although T-cell therapy is a remarkable breakthrough in cancer immunotherapy, the therapeutic efficacy is limited for solid tumors. A major cause of the low efficacy is T-cell exhaustion by immunosuppressive mechanisms of solid tumors, which are mainly mediated by programmed death-ligand 1 (PD-L1) and transforming growth factor-beta (TGF-beta). Herein, T-cell-derived nanovesicles (TCNVs) produced by the serial extrusion of cytotoxic T cells through membranes with micro-/nanosized pores that inhibit T-cell exhaustion and exhibit antitumoral activity maintained in the immunosuppressive tumor microenvironment (TME) are presented. TCNVs, which have programmed cell death protein 1 and TGF-beta receptor on their surface, block PD-L1 on cancer cells and scavenge TGF-beta in the immunosuppressive TME, thereby preventing cytotoxic-T-cell exhaustion. In addition, TCNVs directly kill cancer cells via granzyme B delivery. TCNVs successfully suppress tumor growth in syngeneic-solid-tumor-bearing mice. Taken together, TCNV offers an effective cancer immunotherapy strategy to overcome the tumor's immunosuppressive mechanisms.
- ISSN
- 0935-9648
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