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...
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my.upm.eprints.797392022-10-31T06:55:57Z http://psasir.upm.edu.my/id/eprint/79739/ 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 Mohammed Alitheen, Noorjahan Banu Syed Najmuddin, Syed Umar Faruq Kalyanasundram, Jeevanathan Chan, Soon Choy Veerakumarasivam, Abhimanyu Chia, Suet Lin Yusoff, Khatijah 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. Nature Publishing Group 2019 Article PeerReviewed Mohamed Amin, Zahiah and Che Ani, Muhamad Alhapis and Tan, Sheau Wei and Yeap, Swee Keong and Mohammed Alitheen, Noorjahan Banu and Syed Najmuddin, Syed Umar Faruq and Kalyanasundram, Jeevanathan and Chan, Soon Choy and Veerakumarasivam, Abhimanyu and Chia, Suet Lin and Yusoff, Khatijah (2019) Evaluation of a recombinant Newcastle disease virus expressing human IL12 against human breast cancer. Scientific Reports, 9 (1). art. no. 13999. ISSN 2045-2322 https://www.nature.com/articles/s41598-019-50222-z 10.1038/s41598-019-50222-z |
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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 |
Mohamed Amin, Zahiah Che Ani, Muhamad Alhapis Tan, Sheau Wei Yeap, Swee Keong Mohammed Alitheen, Noorjahan Banu Syed Najmuddin, Syed Umar Faruq Kalyanasundram, Jeevanathan Chan, Soon Choy Veerakumarasivam, Abhimanyu Chia, Suet Lin Yusoff, Khatijah |
spellingShingle |
Mohamed Amin, Zahiah Che Ani, Muhamad Alhapis Tan, Sheau Wei Yeap, Swee Keong Mohammed Alitheen, Noorjahan Banu Syed Najmuddin, Syed Umar Faruq Kalyanasundram, Jeevanathan Chan, Soon Choy Veerakumarasivam, Abhimanyu Chia, Suet Lin Yusoff, Khatijah Evaluation of a recombinant Newcastle disease virus expressing human IL12 against human breast cancer |
author_facet |
Mohamed Amin, Zahiah Che Ani, Muhamad Alhapis Tan, Sheau Wei Yeap, Swee Keong Mohammed Alitheen, Noorjahan Banu Syed Najmuddin, Syed Umar Faruq Kalyanasundram, Jeevanathan Chan, Soon Choy Veerakumarasivam, Abhimanyu Chia, Suet Lin Yusoff, Khatijah |
author_sort |
Mohamed Amin, Zahiah |
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 Publishing Group |
publishDate |
2019 |
url |
http://psasir.upm.edu.my/id/eprint/79739/ https://www.nature.com/articles/s41598-019-50222-z |
_version_ |
1748704618449207296 |