Co-Delivery of the Human NY-ESO-1 Tumor-Associated Antigen and Alpha-GalactosylCeramide by Filamentous Bacteriophages Strongly Enhances the Expansion of Tumor-Specific CD8+ T Cells
Tumor-associated antigens (TAAs) represent attractive targets in the development of anti-cancer vaccines. The filamentous bacteriophage is a safe and versatile delivery nanosystem, and recombinant bacteriophages expressing TAA-derived peptides at a high density on the viral coat proteins improve TAA...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/15/3/672 |
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| author | Roberta Manco Luciana D’Apice Maria Trovato Lucia Lione Erika Salvatori Eleonora Pinto Mirco Compagnone Luigi Aurisicchio Piergiuseppe De Berardinis Rossella Sartorius |
| author_facet | Roberta Manco Luciana D’Apice Maria Trovato Lucia Lione Erika Salvatori Eleonora Pinto Mirco Compagnone Luigi Aurisicchio Piergiuseppe De Berardinis Rossella Sartorius |
| author_sort | Roberta Manco |
| collection | DOAJ |
| description | Tumor-associated antigens (TAAs) represent attractive targets in the development of anti-cancer vaccines. The filamentous bacteriophage is a safe and versatile delivery nanosystem, and recombinant bacteriophages expressing TAA-derived peptides at a high density on the viral coat proteins improve TAA immunogenicity, triggering effective in vivo anti-tumor responses. To enhance the efficacy of the bacteriophage as an anti-tumor vaccine, we designed and generated phage particles expressing a CD8+ peptide derived from the human cancer germline antigen NY-ESO-1 decorated with the immunologically active lipid alpha-GalactosylCeramide (α-GalCer), a potent activator of invariant natural killer T (iNKT) cells. The immune response to phage expressing the human TAA NY-ESO-1 and delivering α-GalCer, namely fdNY-ESO-1/α-GalCer, was analyzed either in vitro or in vivo, using an HLA-A2 transgenic mouse model (HHK). By using NY-ESO-1-specific TCR-engineered T cells and iNKT hybridoma cells, we observed the efficacy of the fdNY-ESO-1/α-GalCer co-delivery strategy at inducing activation of both the cell subsets. Moreover, in vivo administration of fdNY-ESO-1 decorated with α-GalCer lipid in the absence of adjuvants strongly enhances the expansion of NY-ESO-1-specific CD8+ T cells in HHK mice. In conclusion, the filamentous bacteriophage delivering TAA-derived peptides and the α-GalCer lipid may represent a novel and promising anti-tumor vaccination strategy. |
| first_indexed | 2024-03-11T05:47:23Z |
| format | Article |
| id | doaj.art-a7c7dcb38a2846869925773016518e12 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-11T05:47:23Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-a7c7dcb38a2846869925773016518e122023-11-17T14:22:43ZengMDPI AGViruses1999-49152023-03-0115367210.3390/v15030672Co-Delivery of the Human NY-ESO-1 Tumor-Associated Antigen and Alpha-GalactosylCeramide by Filamentous Bacteriophages Strongly Enhances the Expansion of Tumor-Specific CD8+ T CellsRoberta Manco0Luciana D’Apice1Maria Trovato2Lucia Lione3Erika Salvatori4Eleonora Pinto5Mirco Compagnone6Luigi Aurisicchio7Piergiuseppe De Berardinis8Rossella Sartorius9Institute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR), 80131 Naples, ItalyInstitute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR), 80131 Naples, ItalyInstitute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR), 80131 Naples, ItalyTakis Biotech, 00128 Rome, ItalyTakis Biotech, 00128 Rome, ItalyTakis Biotech, 00128 Rome, ItalyTakis Biotech, 00128 Rome, ItalyTakis Biotech, 00128 Rome, ItalyInstitute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR), 80131 Naples, ItalyInstitute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR), 80131 Naples, ItalyTumor-associated antigens (TAAs) represent attractive targets in the development of anti-cancer vaccines. The filamentous bacteriophage is a safe and versatile delivery nanosystem, and recombinant bacteriophages expressing TAA-derived peptides at a high density on the viral coat proteins improve TAA immunogenicity, triggering effective in vivo anti-tumor responses. To enhance the efficacy of the bacteriophage as an anti-tumor vaccine, we designed and generated phage particles expressing a CD8+ peptide derived from the human cancer germline antigen NY-ESO-1 decorated with the immunologically active lipid alpha-GalactosylCeramide (α-GalCer), a potent activator of invariant natural killer T (iNKT) cells. The immune response to phage expressing the human TAA NY-ESO-1 and delivering α-GalCer, namely fdNY-ESO-1/α-GalCer, was analyzed either in vitro or in vivo, using an HLA-A2 transgenic mouse model (HHK). By using NY-ESO-1-specific TCR-engineered T cells and iNKT hybridoma cells, we observed the efficacy of the fdNY-ESO-1/α-GalCer co-delivery strategy at inducing activation of both the cell subsets. Moreover, in vivo administration of fdNY-ESO-1 decorated with α-GalCer lipid in the absence of adjuvants strongly enhances the expansion of NY-ESO-1-specific CD8+ T cells in HHK mice. In conclusion, the filamentous bacteriophage delivering TAA-derived peptides and the α-GalCer lipid may represent a novel and promising anti-tumor vaccination strategy.https://www.mdpi.com/1999-4915/15/3/672filamentous bacteriophageNY-ESO-1iNKTCD8+ T cellalpha-GalactosylCeramidevaccine |
| spellingShingle | Roberta Manco Luciana D’Apice Maria Trovato Lucia Lione Erika Salvatori Eleonora Pinto Mirco Compagnone Luigi Aurisicchio Piergiuseppe De Berardinis Rossella Sartorius Co-Delivery of the Human NY-ESO-1 Tumor-Associated Antigen and Alpha-GalactosylCeramide by Filamentous Bacteriophages Strongly Enhances the Expansion of Tumor-Specific CD8+ T Cells Viruses filamentous bacteriophage NY-ESO-1 iNKT CD8+ T cell alpha-GalactosylCeramide vaccine |
| title | Co-Delivery of the Human NY-ESO-1 Tumor-Associated Antigen and Alpha-GalactosylCeramide by Filamentous Bacteriophages Strongly Enhances the Expansion of Tumor-Specific CD8+ T Cells |
| title_full | Co-Delivery of the Human NY-ESO-1 Tumor-Associated Antigen and Alpha-GalactosylCeramide by Filamentous Bacteriophages Strongly Enhances the Expansion of Tumor-Specific CD8+ T Cells |
| title_fullStr | Co-Delivery of the Human NY-ESO-1 Tumor-Associated Antigen and Alpha-GalactosylCeramide by Filamentous Bacteriophages Strongly Enhances the Expansion of Tumor-Specific CD8+ T Cells |
| title_full_unstemmed | Co-Delivery of the Human NY-ESO-1 Tumor-Associated Antigen and Alpha-GalactosylCeramide by Filamentous Bacteriophages Strongly Enhances the Expansion of Tumor-Specific CD8+ T Cells |
| title_short | Co-Delivery of the Human NY-ESO-1 Tumor-Associated Antigen and Alpha-GalactosylCeramide by Filamentous Bacteriophages Strongly Enhances the Expansion of Tumor-Specific CD8+ T Cells |
| title_sort | co delivery of the human ny eso 1 tumor associated antigen and alpha galactosylceramide by filamentous bacteriophages strongly enhances the expansion of tumor specific cd8 t cells |
| topic | filamentous bacteriophage NY-ESO-1 iNKT CD8+ T cell alpha-GalactosylCeramide vaccine |
| url | https://www.mdpi.com/1999-4915/15/3/672 |
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