Introduction/Background T cell therapy, including adoptive T cell transfer and immune checkpoint blockades, is a remarkable advance in cancer immunotherapy, but its therapeutic effect on solid tumors is limited. A main cause of the low efficacy is T-cell exhaustion by immunosuppressive mechanisms of solid tumors, which are mainly mediated by PD-L1. To address some of the challenges faced by the current cancer mmunotherapy, we developed human T-cell-derived nanovesicles using a perfusable vascular network hydrogel with culturing patient tissues.
Methodology Human T-cell-derived nanovesicles produced by the serial extrusion of human cytotoxic T cells through membranes with nanosized pores that inhibit T-cell exhaustion and exhibit antitumoral activity maintained in the immunosuppressive tumor microenvironment are presented.
Results Similar to cytotoxic T cells, human T-cell-derived nanovesicles can be targeted at tumors via T-cell-membrane-originated proteins and kill cancer cells by releasing anticancer molecules such as granzyme B. Unlike cytotoxic T cells, human T-cell-derived nanovesicles are resistant to immunosuppressive molecules (e.g. PD-L1) of cancer cells by scavenging PD-L1, thereby preventing cytotoxic-T-cell exhaustion. Human T-cell-derived nanovesicles successfully inhibit tumor growth in a 3D human endometrial cancer chip using a perfusable vascular network hydrogel with culturing the same patients‘ tissues. Indeed, human T-cell-derived nanovesicles exhibit higher therapeutic efficacy than an immune checkpoint blockade in endometrial treatment.
Conclusion We propose to present these aspects of the human T-cell-derived nanovesicle to eventually improve the current cancer immunotherapy strategy and overcome the tumor’s immunosuppressive mechanisms.
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