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TRAIL Coated Genetically Engineered Immunotherapeutic Nano-Ghosts Vesicles Target Human Melanoma-Avoiding the Need for High Effective Therapeutic Concentration of TRAIL

Levy, L; Davidov, T; Kolluri, KK; Fridman, A; Krishtul, S; Janes, SM; Machluf, M; (2022) TRAIL Coated Genetically Engineered Immunotherapeutic Nano-Ghosts Vesicles Target Human Melanoma-Avoiding the Need for High Effective Therapeutic Concentration of TRAIL. Advanced Functional Materials , 32 (1) , Article 2105701. 10.1002/adfm.202105701. Green open access

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Abstract

Cancer cell therapy using cytotoxic T lymphocytes (CTL) or mesenchymal stem cells (MSC) possesses hurdles due to the cells, susceptibility to host induced changes. Here, versatile inanimate broadly applicable nanovesicles, termed immunotherapeutic-nano-ghosts (iNGs), are armed with inherent surface-associated targeting and therapeutic capabilities in which the promise and benefits of MSC therapy and T cell immunotherapy are combined into one powerful off-the-shelf approach for treating malignant diseases. To mimic the cytotoxic or immunosuppressive functions of T cells, iNG are produced from MSC that were genetically engineered (GE) or metabolically manipulated to express additional membrane-bound proteins, endowing the NGs derived therefrom with additional surface-associated functions such as tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL). iNGs from GE-MSCs (GE-iNGs) show superior TRAIL retention and induce apoptosis in different cancer cell lines in vitro. In vivo studies on a human melanoma model demonstrate that a systemic, three-day frequency, administration of GE-iNGs result in tumor inhibition comparable to a six orders of magnitude higher concentration of soluble TRAIL. The iNGs are therefore a promising nanovesicle platform that can affect tumors in a non-immunogenic manner while avoiding the need for a highly effective therapeutic concentration.

Type: Article
Title: TRAIL Coated Genetically Engineered Immunotherapeutic Nano-Ghosts Vesicles Target Human Melanoma-Avoiding the Need for High Effective Therapeutic Concentration of TRAIL
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/adfm.202105701
Publisher version: https://doi.org/10.1002/adfm.202105701
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
Keywords: melanoma; mesenchymal stem cells; nano-ghosts; nanovesicles; TRAIL
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Respiratory Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10139303
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