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A Second-Generation Nanoluc-IL27 Fusion Cytokine for Targeted-Gene-Therapy Applications
An emerging approach in treating skeletal malignancies utilizes osteoimmunology to investigate new multifunctional immune-stimulatory agents that can simultaneously combat tumor growth and promote bone repair. We have hypothesized that cytokine Interleukin-27 (IL-27) is an excellent candidate biolog...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8868604/ https://www.ncbi.nlm.nih.gov/pubmed/35200430 http://dx.doi.org/10.3390/bioengineering9020077 |
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author | Salameh, Janelle Wesleyn Kumar, Shreya Rivera-Cruz, Cosette Marie Figueiredo, Marxa Leao |
author_facet | Salameh, Janelle Wesleyn Kumar, Shreya Rivera-Cruz, Cosette Marie Figueiredo, Marxa Leao |
author_sort | Salameh, Janelle Wesleyn |
collection | PubMed |
description | An emerging approach in treating skeletal malignancies utilizes osteoimmunology to investigate new multifunctional immune-stimulatory agents that can simultaneously combat tumor growth and promote bone repair. We have hypothesized that cytokine Interleukin-27 (IL-27) is an excellent candidate biologic to help rebalance the prostate tumor cells and bone cell environment. In this work, we examined the proof of principle for a short, secreted luciferase (Nanoluc or Nluc) fusion with IL-27 to produce a novel cytokine-based biologic (Nluc-27), whereby we examined its efficacy in vitro in reducing prostate tumor growth and rebalancing bone cell proliferation and differentiation. This work demonstrates the targeting and anti-tumor efficacy of the Nluc-27 fusion cytokine in cancer and bone cell models. The fusion cytokine is detectable in conditioned media, and bioactive in different cell systems. This novel Nluc-27 cytokine will allow flexible incorporation of other targeting domains and may serve as flexible tool to augment IL-27′s bioactivity and reengineer its efficacy against prostate tumor or bone cells, and may prove applicable to several other cell types for targeted gene therapy applications. |
format | Online Article Text |
id | pubmed-8868604 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-88686042022-02-25 A Second-Generation Nanoluc-IL27 Fusion Cytokine for Targeted-Gene-Therapy Applications Salameh, Janelle Wesleyn Kumar, Shreya Rivera-Cruz, Cosette Marie Figueiredo, Marxa Leao Bioengineering (Basel) Article An emerging approach in treating skeletal malignancies utilizes osteoimmunology to investigate new multifunctional immune-stimulatory agents that can simultaneously combat tumor growth and promote bone repair. We have hypothesized that cytokine Interleukin-27 (IL-27) is an excellent candidate biologic to help rebalance the prostate tumor cells and bone cell environment. In this work, we examined the proof of principle for a short, secreted luciferase (Nanoluc or Nluc) fusion with IL-27 to produce a novel cytokine-based biologic (Nluc-27), whereby we examined its efficacy in vitro in reducing prostate tumor growth and rebalancing bone cell proliferation and differentiation. This work demonstrates the targeting and anti-tumor efficacy of the Nluc-27 fusion cytokine in cancer and bone cell models. The fusion cytokine is detectable in conditioned media, and bioactive in different cell systems. This novel Nluc-27 cytokine will allow flexible incorporation of other targeting domains and may serve as flexible tool to augment IL-27′s bioactivity and reengineer its efficacy against prostate tumor or bone cells, and may prove applicable to several other cell types for targeted gene therapy applications. MDPI 2022-02-16 /pmc/articles/PMC8868604/ /pubmed/35200430 http://dx.doi.org/10.3390/bioengineering9020077 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Salameh, Janelle Wesleyn Kumar, Shreya Rivera-Cruz, Cosette Marie Figueiredo, Marxa Leao A Second-Generation Nanoluc-IL27 Fusion Cytokine for Targeted-Gene-Therapy Applications |
title | A Second-Generation Nanoluc-IL27 Fusion Cytokine for Targeted-Gene-Therapy Applications |
title_full | A Second-Generation Nanoluc-IL27 Fusion Cytokine for Targeted-Gene-Therapy Applications |
title_fullStr | A Second-Generation Nanoluc-IL27 Fusion Cytokine for Targeted-Gene-Therapy Applications |
title_full_unstemmed | A Second-Generation Nanoluc-IL27 Fusion Cytokine for Targeted-Gene-Therapy Applications |
title_short | A Second-Generation Nanoluc-IL27 Fusion Cytokine for Targeted-Gene-Therapy Applications |
title_sort | second-generation nanoluc-il27 fusion cytokine for targeted-gene-therapy applications |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8868604/ https://www.ncbi.nlm.nih.gov/pubmed/35200430 http://dx.doi.org/10.3390/bioengineering9020077 |
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