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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...

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Autores principales: Salameh, Janelle Wesleyn, Kumar, Shreya, Rivera-Cruz, Cosette Marie, Figueiredo, Marxa Leao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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