Evaluation of a Recombinant Newcastle Disease Virus Expressing Human IL12 against Human Breast Cancer

Abstract 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...

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Autores principales:	Zahiah Mohamed Amin, Muhamad Alhapis Che Ani, Sheau Wei Tan, Swee Keong Yeap, Noorjahan Banu Alitheen, Syed Umar Faruq Syed Najmuddin, Jeevanathan Kalyanasundram, Soon Choy Chan, Abhi Veerakumarasivam, Suet Lin Chia, Khatijah Yusoff
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f8373010fc52448aa4c9cec3b38903fd
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spelling	oai:doaj.org-article:f8373010fc52448aa4c9cec3b38903fd2021-12-02T15:08:30ZEvaluation of a Recombinant Newcastle Disease Virus Expressing Human IL12 against Human Breast Cancer10.1038/s41598-019-50222-z2045-2322https://doaj.org/article/f8373010fc52448aa4c9cec3b38903fd2019-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-50222-zhttps://doaj.org/toc/2045-2322Abstract 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 29. 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.Zahiah Mohamed AminMuhamad Alhapis Che AniSheau Wei TanSwee Keong YeapNoorjahan Banu AlitheenSyed Umar Faruq Syed NajmuddinJeevanathan KalyanasundramSoon Choy ChanAbhi VeerakumarasivamSuet Lin ChiaKhatijah YusoffNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-10 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Zahiah Mohamed Amin Muhamad Alhapis Che Ani Sheau Wei Tan Swee Keong Yeap Noorjahan Banu Alitheen Syed Umar Faruq Syed Najmuddin Jeevanathan Kalyanasundram Soon Choy Chan Abhi Veerakumarasivam Suet Lin Chia Khatijah Yusoff Evaluation of a Recombinant Newcastle Disease Virus Expressing Human IL12 against Human Breast Cancer
description	Abstract 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 29. 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	article
author	Zahiah Mohamed Amin Muhamad Alhapis Che Ani Sheau Wei Tan Swee Keong Yeap Noorjahan Banu Alitheen Syed Umar Faruq Syed Najmuddin Jeevanathan Kalyanasundram Soon Choy Chan Abhi Veerakumarasivam Suet Lin Chia Khatijah Yusoff
author_facet	Zahiah Mohamed Amin Muhamad Alhapis Che Ani Sheau Wei Tan Swee Keong Yeap Noorjahan Banu Alitheen Syed Umar Faruq Syed Najmuddin Jeevanathan Kalyanasundram Soon Choy Chan Abhi Veerakumarasivam Suet Lin Chia Khatijah Yusoff
author_sort	Zahiah Mohamed Amin
title	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_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_sort	evaluation of a recombinant newcastle disease virus expressing human il12 against human breast cancer
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/f8373010fc52448aa4c9cec3b38903fd
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Evaluation of a Recombinant Newcastle Disease Virus Expressing Human IL12 against Human Breast Cancer

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