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Evaluation of a Recombinant Newcastle Disease Virus Expressing Human IL12 against Human Breast Cancer
The Newcastle disease virus (NDV) strain AF2240 is an avian avulavirus that has been demonstrated to possess oncolytic activity against cancer cells. However, to illicit a greater anti-cancer immune response, it is believed that the incorporation of immunostimulatory genes such as IL12 into a recomb...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768883/ https://www.ncbi.nlm.nih.gov/pubmed/31570732 http://dx.doi.org/10.1038/s41598-019-50222-z |
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author | Mohamed Amin, Zahiah Che Ani, Muhamad Alhapis Tan, Sheau Wei Yeap, Swee Keong Alitheen, Noorjahan Banu Syed Najmuddin, Syed Umar Faruq Kalyanasundram, Jeevanathan Chan, Soon Choy Veerakumarasivam, Abhi Chia, Suet Lin Yusoff, Khatijah |
author_facet | Mohamed Amin, Zahiah Che Ani, Muhamad Alhapis Tan, Sheau Wei Yeap, Swee Keong Alitheen, Noorjahan Banu Syed Najmuddin, Syed Umar Faruq Kalyanasundram, Jeevanathan Chan, Soon Choy Veerakumarasivam, Abhi Chia, Suet Lin Yusoff, Khatijah |
author_sort | Mohamed Amin, Zahiah |
collection | PubMed |
description | The Newcastle disease virus (NDV) strain AF2240 is an avian avulavirus that has been demonstrated to possess oncolytic activity against cancer cells. However, to illicit a greater anti-cancer immune response, it is believed that the incorporation of immunostimulatory genes such as IL12 into a recombinant NDV backbone will enhance its oncolytic effect. In this study, a newly developed recombinant NDV that expresses IL12 (rAF-IL12) was tested for its safety, stability and cytotoxicity. The stability of rAF-IL12 was maintained when passaged in specific pathogen free (SPF) chicken eggs from passage 1 to passage 10; with an HA titer of 2(9). Based on the results obtained from the MTT cytotoxic assay, rAF-IL12 was determined to be safe as it only induced cytotoxic effects against normal chicken cell lines and human breast cancer cells while sparing normal cells. Significant tumor growth inhibition (52%) was observed in the rAF-IL12-treated mice. The in vivo safety profile of rAF-IL12 was confirmed through histological observation and viral load titer assay. The concentration and presence of the expressed IL12 was quantified and verified via ELISA assay. In summary, rAF-IL12 was proven to be safe, selectively replicating in chicken and cancer cells and was able to maintain its stability throughout several passages; thus enhancing its potential as an anti-breast cancer vaccine. |
format | Online Article Text |
id | pubmed-6768883 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-67688832019-10-04 Evaluation of a Recombinant Newcastle Disease Virus Expressing Human IL12 against Human Breast Cancer Mohamed Amin, Zahiah Che Ani, Muhamad Alhapis Tan, Sheau Wei Yeap, Swee Keong Alitheen, Noorjahan Banu Syed Najmuddin, Syed Umar Faruq Kalyanasundram, Jeevanathan Chan, Soon Choy Veerakumarasivam, Abhi Chia, Suet Lin Yusoff, Khatijah Sci Rep Article The Newcastle disease virus (NDV) strain AF2240 is an avian avulavirus that has been demonstrated to possess oncolytic activity against cancer cells. However, to illicit a greater anti-cancer immune response, it is believed that the incorporation of immunostimulatory genes such as IL12 into a recombinant NDV backbone will enhance its oncolytic effect. In this study, a newly developed recombinant NDV that expresses IL12 (rAF-IL12) was tested for its safety, stability and cytotoxicity. The stability of rAF-IL12 was maintained when passaged in specific pathogen free (SPF) chicken eggs from passage 1 to passage 10; with an HA titer of 2(9). Based on the results obtained from the MTT cytotoxic assay, rAF-IL12 was determined to be safe as it only induced cytotoxic effects against normal chicken cell lines and human breast cancer cells while sparing normal cells. Significant tumor growth inhibition (52%) was observed in the rAF-IL12-treated mice. The in vivo safety profile of rAF-IL12 was confirmed through histological observation and viral load titer assay. The concentration and presence of the expressed IL12 was quantified and verified via ELISA assay. In summary, rAF-IL12 was proven to be safe, selectively replicating in chicken and cancer cells and was able to maintain its stability throughout several passages; thus enhancing its potential as an anti-breast cancer vaccine. Nature Publishing Group UK 2019-09-30 /pmc/articles/PMC6768883/ /pubmed/31570732 http://dx.doi.org/10.1038/s41598-019-50222-z Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Mohamed Amin, Zahiah Che Ani, Muhamad Alhapis Tan, Sheau Wei Yeap, Swee Keong Alitheen, Noorjahan Banu Syed Najmuddin, Syed Umar Faruq Kalyanasundram, Jeevanathan Chan, Soon Choy Veerakumarasivam, Abhi Chia, Suet Lin Yusoff, Khatijah Evaluation of a Recombinant Newcastle Disease Virus Expressing Human IL12 against Human Breast Cancer |
title | Evaluation of a Recombinant Newcastle Disease Virus Expressing Human IL12 against Human Breast Cancer |
title_full | Evaluation of a Recombinant Newcastle Disease Virus Expressing Human IL12 against Human Breast Cancer |
title_fullStr | Evaluation of a Recombinant Newcastle Disease Virus Expressing Human IL12 against Human Breast Cancer |
title_full_unstemmed | Evaluation of a Recombinant Newcastle Disease Virus Expressing Human IL12 against Human Breast Cancer |
title_short | Evaluation of a Recombinant Newcastle Disease Virus Expressing Human IL12 against Human Breast Cancer |
title_sort | evaluation of a recombinant newcastle disease virus expressing human il12 against human breast cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768883/ https://www.ncbi.nlm.nih.gov/pubmed/31570732 http://dx.doi.org/10.1038/s41598-019-50222-z |
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