Tackling suppressive cancer microenvironment by NARF-derived immune modulatory vaccine and its validation using simulation strategies
Introduction: Targeting tumor microenvironment is beneficial and present an ideal setting for the development of futuristic immunotherapy. Here, we make use of Nuclear prelamin A recognition factor (NARF), a protein linked to the coactivation of transcriptional regulators in human breast cancer stem...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Physics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphy.2024.1342115/full |
| _version_ | 1797300265571844096 |
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| author | Priyanga Paranthaman Shanthi Veerappapillai |
| author_facet | Priyanga Paranthaman Shanthi Veerappapillai |
| author_sort | Priyanga Paranthaman |
| collection | DOAJ |
| description | Introduction: Targeting tumor microenvironment is beneficial and present an ideal setting for the development of futuristic immunotherapy. Here, we make use of Nuclear prelamin A recognition factor (NARF), a protein linked to the coactivation of transcriptional regulators in human breast cancer stem cells (CSC) in our investigation.Methods: In this study, we initially computed the epitope regions possessing the ability to stimulate both T and B cells within the NARF protein. These identified epitope areas were fused with an adjuvant such as RpfB and RpfE as well as linkers like AAY, GPGPG, KK, and EAAAK. The constructed vaccine was further characterized by assessing its physicochemical properties and population coverage. The potential interactions of the designed vaccine with different toll-like receptors were examined by a sequence of computational studies. Of note, docking study were employed to understand its mechanism of action. Molecular dynamics and immune simulation studies were conducted to comprehend more into their structural stability and immune responses. The resultant vaccine was back-translated, codon-optimised and introduced into pET-28 (+) vector.Results and discussion: We hypothesize from the results that the designed NARF protein-based vaccine in our analysis could effectively provoke the immune responses in the target organism through TLR-7 binding and promotes MHC class-II mediated antigen presentation. Indeed, comprehensive evaluations conducted in both in vitro and in vivo settings are imperative to substantiate the safety and efficacy of the developed vaccine. |
| first_indexed | 2024-03-07T23:04:46Z |
| format | Article |
| id | doaj.art-0d6b0b15bbc6426c89447db7c52cdffe |
| institution | Directory Open Access Journal |
| issn | 2296-424X |
| language | English |
| last_indexed | 2024-03-07T23:04:46Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physics |
| spelling | doaj.art-0d6b0b15bbc6426c89447db7c52cdffe2024-02-22T05:11:20ZengFrontiers Media S.A.Frontiers in Physics2296-424X2024-02-011210.3389/fphy.2024.13421151342115Tackling suppressive cancer microenvironment by NARF-derived immune modulatory vaccine and its validation using simulation strategiesPriyanga ParanthamanShanthi VeerappapillaiIntroduction: Targeting tumor microenvironment is beneficial and present an ideal setting for the development of futuristic immunotherapy. Here, we make use of Nuclear prelamin A recognition factor (NARF), a protein linked to the coactivation of transcriptional regulators in human breast cancer stem cells (CSC) in our investigation.Methods: In this study, we initially computed the epitope regions possessing the ability to stimulate both T and B cells within the NARF protein. These identified epitope areas were fused with an adjuvant such as RpfB and RpfE as well as linkers like AAY, GPGPG, KK, and EAAAK. The constructed vaccine was further characterized by assessing its physicochemical properties and population coverage. The potential interactions of the designed vaccine with different toll-like receptors were examined by a sequence of computational studies. Of note, docking study were employed to understand its mechanism of action. Molecular dynamics and immune simulation studies were conducted to comprehend more into their structural stability and immune responses. The resultant vaccine was back-translated, codon-optimised and introduced into pET-28 (+) vector.Results and discussion: We hypothesize from the results that the designed NARF protein-based vaccine in our analysis could effectively provoke the immune responses in the target organism through TLR-7 binding and promotes MHC class-II mediated antigen presentation. Indeed, comprehensive evaluations conducted in both in vitro and in vivo settings are imperative to substantiate the safety and efficacy of the developed vaccine.https://www.frontiersin.org/articles/10.3389/fphy.2024.1342115/fullnuclear prelamin a recognition factorcancersnext-generation vaccineimmunotherapydockingdynamics simulations |
| spellingShingle | Priyanga Paranthaman Shanthi Veerappapillai Tackling suppressive cancer microenvironment by NARF-derived immune modulatory vaccine and its validation using simulation strategies Frontiers in Physics nuclear prelamin a recognition factor cancers next-generation vaccine immunotherapy docking dynamics simulations |
| title | Tackling suppressive cancer microenvironment by NARF-derived immune modulatory vaccine and its validation using simulation strategies |
| title_full | Tackling suppressive cancer microenvironment by NARF-derived immune modulatory vaccine and its validation using simulation strategies |
| title_fullStr | Tackling suppressive cancer microenvironment by NARF-derived immune modulatory vaccine and its validation using simulation strategies |
| title_full_unstemmed | Tackling suppressive cancer microenvironment by NARF-derived immune modulatory vaccine and its validation using simulation strategies |
| title_short | Tackling suppressive cancer microenvironment by NARF-derived immune modulatory vaccine and its validation using simulation strategies |
| title_sort | tackling suppressive cancer microenvironment by narf derived immune modulatory vaccine and its validation using simulation strategies |
| topic | nuclear prelamin a recognition factor cancers next-generation vaccine immunotherapy docking dynamics simulations |
| url | https://www.frontiersin.org/articles/10.3389/fphy.2024.1342115/full |
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