Cargando…
Synergy between hemagglutinin 2 (HA2) subunit of influenza fusogenic membrane glycoprotein and oncolytic Newcastle disease virus suppressed tumor growth and further enhanced by Immune checkpoint PD-1 blockade
BACKGROUND: Newcastle disease virus (NDV) has shown noticeable oncolytic properties, especially against cervical cancer. However, in order to improve the spread rate and oncotoxicity of the virus, employment of other therapeutic reagents would be helpful. It has been shown that some viral fusogenic...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412675/ https://www.ncbi.nlm.nih.gov/pubmed/32782438 http://dx.doi.org/10.1186/s12935-020-01476-5 |
_version_ | 1783568658788777984 |
---|---|
author | Miri, Seyed Mohammad Ebrahimzadeh, Mir Saeed Abdolalipour, Elahe Yazdi, Mahsa Hosseini Ravandi, Hassan Ghaemi, Amir |
author_facet | Miri, Seyed Mohammad Ebrahimzadeh, Mir Saeed Abdolalipour, Elahe Yazdi, Mahsa Hosseini Ravandi, Hassan Ghaemi, Amir |
author_sort | Miri, Seyed Mohammad |
collection | PubMed |
description | BACKGROUND: Newcastle disease virus (NDV) has shown noticeable oncolytic properties, especially against cervical cancer. However, in order to improve the spread rate and oncotoxicity of the virus, employment of other therapeutic reagents would be helpful. It has been shown that some viral fusogenic membrane glycoproteins (FMGs) could facilitate viral propagation and increase the infection rate of tumor cells by oncolytic viruses. Additionally, immune checkpoint blockade has widely been investigated for its anti-tumor effects against several types of cancers. Here, we investigated for the first time whether the incorporation of influenza hemagglutinin-2 (HA2) FMG could improve the oncolytic characteristics of NDV against cervical cancer. Next, we added anti-PD-1 mAb to our therapeutic recipe to assess the complementary role of immune checkpoint blockade in curbing tumor progression. METHODS: For this purpose, TC-1 tumor cells were injected into the mice models and treatment with NDV, iNDV, HA2, NDV-HA2, iNDV-HA2 began 10 days after tumor challenge and was repeated at day 17. In addition, PD-1 blockade was conducted by injection of anti-PD-1 mAb at days 9 and 16. Two weeks after the last treatment, sample mice were sacrificed and treatment efficacy was evaluated through immunological and immunohistochemical analysis. Moreover, tumors condition was monitored weekly for 6 weeks intervals and the tumor volume was measured and compared within different groups. RESULTS: The results of co-treatment with NDV and HA2 gene revealed that these agents act synergistically to induce antitumor immune responses against HPV-associated carcinoma by enhancement of E7-specific lymphocyte proliferation, inducement of CD8(+) T cell cytotoxicity responses, increase in splenic cytokines and granzyme B, decrease in immunosuppressive cytokines and E6 oncogene expression, and upregulation of apoptotic proteins expression, in comparison with control groups. Moreover, incorporation of PD-1 blockade as the third side of our suggested therapy led to noticeable regression in tumor size and augmentation of cytokine responses. CONCLUSIONS: The invaluable results of synergy between NDV virotherapy and HA2 gene therapy suggest that tumor-selective cell killing by oncolytic NDV can be enhanced by combining with FMG gene therapy. Moreover, the adjunction of the PD-1 blockade proves that checkpoint blockade can be considered as an effective complementary therapy for the treatment of cervical cancer. |
format | Online Article Text |
id | pubmed-7412675 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-74126752020-08-10 Synergy between hemagglutinin 2 (HA2) subunit of influenza fusogenic membrane glycoprotein and oncolytic Newcastle disease virus suppressed tumor growth and further enhanced by Immune checkpoint PD-1 blockade Miri, Seyed Mohammad Ebrahimzadeh, Mir Saeed Abdolalipour, Elahe Yazdi, Mahsa Hosseini Ravandi, Hassan Ghaemi, Amir Cancer Cell Int Primary Research BACKGROUND: Newcastle disease virus (NDV) has shown noticeable oncolytic properties, especially against cervical cancer. However, in order to improve the spread rate and oncotoxicity of the virus, employment of other therapeutic reagents would be helpful. It has been shown that some viral fusogenic membrane glycoproteins (FMGs) could facilitate viral propagation and increase the infection rate of tumor cells by oncolytic viruses. Additionally, immune checkpoint blockade has widely been investigated for its anti-tumor effects against several types of cancers. Here, we investigated for the first time whether the incorporation of influenza hemagglutinin-2 (HA2) FMG could improve the oncolytic characteristics of NDV against cervical cancer. Next, we added anti-PD-1 mAb to our therapeutic recipe to assess the complementary role of immune checkpoint blockade in curbing tumor progression. METHODS: For this purpose, TC-1 tumor cells were injected into the mice models and treatment with NDV, iNDV, HA2, NDV-HA2, iNDV-HA2 began 10 days after tumor challenge and was repeated at day 17. In addition, PD-1 blockade was conducted by injection of anti-PD-1 mAb at days 9 and 16. Two weeks after the last treatment, sample mice were sacrificed and treatment efficacy was evaluated through immunological and immunohistochemical analysis. Moreover, tumors condition was monitored weekly for 6 weeks intervals and the tumor volume was measured and compared within different groups. RESULTS: The results of co-treatment with NDV and HA2 gene revealed that these agents act synergistically to induce antitumor immune responses against HPV-associated carcinoma by enhancement of E7-specific lymphocyte proliferation, inducement of CD8(+) T cell cytotoxicity responses, increase in splenic cytokines and granzyme B, decrease in immunosuppressive cytokines and E6 oncogene expression, and upregulation of apoptotic proteins expression, in comparison with control groups. Moreover, incorporation of PD-1 blockade as the third side of our suggested therapy led to noticeable regression in tumor size and augmentation of cytokine responses. CONCLUSIONS: The invaluable results of synergy between NDV virotherapy and HA2 gene therapy suggest that tumor-selective cell killing by oncolytic NDV can be enhanced by combining with FMG gene therapy. Moreover, the adjunction of the PD-1 blockade proves that checkpoint blockade can be considered as an effective complementary therapy for the treatment of cervical cancer. BioMed Central 2020-08-07 /pmc/articles/PMC7412675/ /pubmed/32782438 http://dx.doi.org/10.1186/s12935-020-01476-5 Text en © The Author(s) 2020 Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Primary Research Miri, Seyed Mohammad Ebrahimzadeh, Mir Saeed Abdolalipour, Elahe Yazdi, Mahsa Hosseini Ravandi, Hassan Ghaemi, Amir Synergy between hemagglutinin 2 (HA2) subunit of influenza fusogenic membrane glycoprotein and oncolytic Newcastle disease virus suppressed tumor growth and further enhanced by Immune checkpoint PD-1 blockade |
title |
Synergy between hemagglutinin 2 (HA2) subunit of influenza fusogenic membrane glycoprotein and oncolytic Newcastle disease virus suppressed tumor growth and further enhanced by Immune checkpoint PD-1 blockade |
title_full |
Synergy between hemagglutinin 2 (HA2) subunit of influenza fusogenic membrane glycoprotein and oncolytic Newcastle disease virus suppressed tumor growth and further enhanced by Immune checkpoint PD-1 blockade |
title_fullStr |
Synergy between hemagglutinin 2 (HA2) subunit of influenza fusogenic membrane glycoprotein and oncolytic Newcastle disease virus suppressed tumor growth and further enhanced by Immune checkpoint PD-1 blockade |
title_full_unstemmed |
Synergy between hemagglutinin 2 (HA2) subunit of influenza fusogenic membrane glycoprotein and oncolytic Newcastle disease virus suppressed tumor growth and further enhanced by Immune checkpoint PD-1 blockade |
title_short |
Synergy between hemagglutinin 2 (HA2) subunit of influenza fusogenic membrane glycoprotein and oncolytic Newcastle disease virus suppressed tumor growth and further enhanced by Immune checkpoint PD-1 blockade |
title_sort | synergy between hemagglutinin 2 (ha2) subunit of influenza fusogenic membrane glycoprotein and oncolytic newcastle disease virus suppressed tumor growth and further enhanced by immune checkpoint pd-1 blockade |
topic | Primary Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412675/ https://www.ncbi.nlm.nih.gov/pubmed/32782438 http://dx.doi.org/10.1186/s12935-020-01476-5 |
work_keys_str_mv | AT miriseyedmohammad synergybetweenhemagglutinin2ha2subunitofinfluenzafusogenicmembraneglycoproteinandoncolyticnewcastlediseasevirussuppressedtumorgrowthandfurtherenhancedbyimmunecheckpointpd1blockade AT ebrahimzadehmirsaeed synergybetweenhemagglutinin2ha2subunitofinfluenzafusogenicmembraneglycoproteinandoncolyticnewcastlediseasevirussuppressedtumorgrowthandfurtherenhancedbyimmunecheckpointpd1blockade AT abdolalipourelahe synergybetweenhemagglutinin2ha2subunitofinfluenzafusogenicmembraneglycoproteinandoncolyticnewcastlediseasevirussuppressedtumorgrowthandfurtherenhancedbyimmunecheckpointpd1blockade AT yazdimahsa synergybetweenhemagglutinin2ha2subunitofinfluenzafusogenicmembraneglycoproteinandoncolyticnewcastlediseasevirussuppressedtumorgrowthandfurtherenhancedbyimmunecheckpointpd1blockade AT hosseiniravandihassan synergybetweenhemagglutinin2ha2subunitofinfluenzafusogenicmembraneglycoproteinandoncolyticnewcastlediseasevirussuppressedtumorgrowthandfurtherenhancedbyimmunecheckpointpd1blockade AT ghaemiamir synergybetweenhemagglutinin2ha2subunitofinfluenzafusogenicmembraneglycoproteinandoncolyticnewcastlediseasevirussuppressedtumorgrowthandfurtherenhancedbyimmunecheckpointpd1blockade |