An Engineered M13 Filamentous Nanoparticle as an Antigen Carrier for a Malignant Melanoma Immunotherapeutic Strategy
Bacteriophages, prokaryotic viruses, hold great potential in genetic engineering to open up new avenues for vaccine development. Our study aimed to establish engineered M13 bacteriophages expressing MAGE-A1 tumor peptides as a vaccine for melanoma treatment. Through in vivo experiments, we sought to...
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MDPI AG
2024-02-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/16/2/232 |
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| author | Nuša Brišar Katja Šuster Simona Kranjc Brezar Robert Vidmar Marko Fonović Andrej Cör |
| author_facet | Nuša Brišar Katja Šuster Simona Kranjc Brezar Robert Vidmar Marko Fonović Andrej Cör |
| author_sort | Nuša Brišar |
| collection | DOAJ |
| description | Bacteriophages, prokaryotic viruses, hold great potential in genetic engineering to open up new avenues for vaccine development. Our study aimed to establish engineered M13 bacteriophages expressing MAGE-A1 tumor peptides as a vaccine for melanoma treatment. Through in vivo experiments, we sought to assess their ability to induce robust immune responses. Using phage display technology, we engineered two M13 bacteriophages expressing MAGE-A1 peptides as fusion proteins with either pVIII or pIIII coat proteins. Mice were intraperitoneally vaccinated three times, two weeks apart, using two different engineered bacteriophages; control groups received a wild-type bacteriophage. Serum samples taken seven days after each vaccination were analyzed by ELISA assay, while splenocytes harvested seven days following the second boost were evaluated by ex vivo cytotoxicity assay. Fusion proteins were confirmed by Western blot and nano-LC-MS/MS. The application of bacteriophages was safe, with no adverse effects on mice. Engineered bacteriophages effectively triggered immune responses, leading to increased levels of anti-MAGE-A1 antibodies in proportion to the administered bacteriophage dosage. Anti-MAGE-A1 antibodies also exhibited a binding capability to B16F10 tumor cells in vitro, as opposed to control samples. Splenocytes demonstrated enhanced CTL cytotoxicity against B16F10 cells. We have demonstrated the immunogenic capabilities of engineered M13 bacteriophages, emphasizing their potential for melanoma immunotherapy. |
| first_indexed | 2024-03-07T22:10:55Z |
| format | Article |
| id | doaj.art-3be89086974a4412a95e536e2e6a0496 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-07T22:10:55Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-3be89086974a4412a95e536e2e6a04962024-02-23T15:37:33ZengMDPI AGViruses1999-49152024-02-0116223210.3390/v16020232An Engineered M13 Filamentous Nanoparticle as an Antigen Carrier for a Malignant Melanoma Immunotherapeutic StrategyNuša Brišar0Katja Šuster1Simona Kranjc Brezar2Robert Vidmar3Marko Fonović4Andrej Cör5Faculty of Health Sciences, University of Primorska, 6310 Izola, SloveniaValdoltra Orthopaedic Hospital, 6280 Ankaran, SloveniaDepartment of Experimental Oncology, Institute of Oncology Ljubljana, 1000 Ljubljana, SloveniaDepartment of Biochemistry, Molecular and Structural Biology, Jozef Stefan Institute, 1000 Ljubljana, SloveniaDepartment of Biochemistry, Molecular and Structural Biology, Jozef Stefan Institute, 1000 Ljubljana, SloveniaValdoltra Orthopaedic Hospital, 6280 Ankaran, SloveniaBacteriophages, prokaryotic viruses, hold great potential in genetic engineering to open up new avenues for vaccine development. Our study aimed to establish engineered M13 bacteriophages expressing MAGE-A1 tumor peptides as a vaccine for melanoma treatment. Through in vivo experiments, we sought to assess their ability to induce robust immune responses. Using phage display technology, we engineered two M13 bacteriophages expressing MAGE-A1 peptides as fusion proteins with either pVIII or pIIII coat proteins. Mice were intraperitoneally vaccinated three times, two weeks apart, using two different engineered bacteriophages; control groups received a wild-type bacteriophage. Serum samples taken seven days after each vaccination were analyzed by ELISA assay, while splenocytes harvested seven days following the second boost were evaluated by ex vivo cytotoxicity assay. Fusion proteins were confirmed by Western blot and nano-LC-MS/MS. The application of bacteriophages was safe, with no adverse effects on mice. Engineered bacteriophages effectively triggered immune responses, leading to increased levels of anti-MAGE-A1 antibodies in proportion to the administered bacteriophage dosage. Anti-MAGE-A1 antibodies also exhibited a binding capability to B16F10 tumor cells in vitro, as opposed to control samples. Splenocytes demonstrated enhanced CTL cytotoxicity against B16F10 cells. We have demonstrated the immunogenic capabilities of engineered M13 bacteriophages, emphasizing their potential for melanoma immunotherapy.https://www.mdpi.com/1999-4915/16/2/232nanoparticlesfilamentous bacteriophagesphage display technologybacteriophage-based vaccinemelanoma-associated antigenmalignant melanoma immunotherapy |
| spellingShingle | Nuša Brišar Katja Šuster Simona Kranjc Brezar Robert Vidmar Marko Fonović Andrej Cör An Engineered M13 Filamentous Nanoparticle as an Antigen Carrier for a Malignant Melanoma Immunotherapeutic Strategy Viruses nanoparticles filamentous bacteriophages phage display technology bacteriophage-based vaccine melanoma-associated antigen malignant melanoma immunotherapy |
| title | An Engineered M13 Filamentous Nanoparticle as an Antigen Carrier for a Malignant Melanoma Immunotherapeutic Strategy |
| title_full | An Engineered M13 Filamentous Nanoparticle as an Antigen Carrier for a Malignant Melanoma Immunotherapeutic Strategy |
| title_fullStr | An Engineered M13 Filamentous Nanoparticle as an Antigen Carrier for a Malignant Melanoma Immunotherapeutic Strategy |
| title_full_unstemmed | An Engineered M13 Filamentous Nanoparticle as an Antigen Carrier for a Malignant Melanoma Immunotherapeutic Strategy |
| title_short | An Engineered M13 Filamentous Nanoparticle as an Antigen Carrier for a Malignant Melanoma Immunotherapeutic Strategy |
| title_sort | engineered m13 filamentous nanoparticle as an antigen carrier for a malignant melanoma immunotherapeutic strategy |
| topic | nanoparticles filamentous bacteriophages phage display technology bacteriophage-based vaccine melanoma-associated antigen malignant melanoma immunotherapy |
| url | https://www.mdpi.com/1999-4915/16/2/232 |
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