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.
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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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