Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
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
_version_ 1783455140031758336
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
work_keys_str_mv AT mohamedaminzahiah evaluationofarecombinantnewcastlediseasevirusexpressinghumanil12againsthumanbreastcancer
AT cheanimuhamadalhapis evaluationofarecombinantnewcastlediseasevirusexpressinghumanil12againsthumanbreastcancer
AT tansheauwei evaluationofarecombinantnewcastlediseasevirusexpressinghumanil12againsthumanbreastcancer
AT yeapsweekeong evaluationofarecombinantnewcastlediseasevirusexpressinghumanil12againsthumanbreastcancer
AT alitheennoorjahanbanu evaluationofarecombinantnewcastlediseasevirusexpressinghumanil12againsthumanbreastcancer
AT syednajmuddinsyedumarfaruq evaluationofarecombinantnewcastlediseasevirusexpressinghumanil12againsthumanbreastcancer
AT kalyanasundramjeevanathan evaluationofarecombinantnewcastlediseasevirusexpressinghumanil12againsthumanbreastcancer
AT chansoonchoy evaluationofarecombinantnewcastlediseasevirusexpressinghumanil12againsthumanbreastcancer
AT veerakumarasivamabhi evaluationofarecombinantnewcastlediseasevirusexpressinghumanil12againsthumanbreastcancer
AT chiasuetlin evaluationofarecombinantnewcastlediseasevirusexpressinghumanil12againsthumanbreastcancer
AT yusoffkhatijah evaluationofarecombinantnewcastlediseasevirusexpressinghumanil12againsthumanbreastcancer