The CD8+ T Cell-Mediated Immunity Induced by HPV-E6 Uploaded in Engineered Exosomes Is Improved by ISCOMATRIXTM Adjuvant
We recently described the induction of an efficient CD8+ T cell-mediated immune response against a tumor-associated antigen (TAA) uploaded in engineered exosomes used as an immunogen delivery tool. This immune response cleared tumor cells inoculated after immunization, and controlled the growth of t...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2016-11-01
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| Series: | Vaccines |
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| Online Access: | http://www.mdpi.com/2076-393X/4/4/42 |
| _version_ | 1811213444298309632 |
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| author | Francesco Manfredi Paola di Bonito Barbara Ridolfi Simona Anticoli Claudia Arenaccio Chiara Chiozzini Adriana Baz Morelli Maurizio Federico |
| author_facet | Francesco Manfredi Paola di Bonito Barbara Ridolfi Simona Anticoli Claudia Arenaccio Chiara Chiozzini Adriana Baz Morelli Maurizio Federico |
| author_sort | Francesco Manfredi |
| collection | DOAJ |
| description | We recently described the induction of an efficient CD8+ T cell-mediated immune response against a tumor-associated antigen (TAA) uploaded in engineered exosomes used as an immunogen delivery tool. This immune response cleared tumor cells inoculated after immunization, and controlled the growth of tumors implanted before immunization. We looked for new protocols aimed at increasing the CD8+ T cell specific response to the antigen uploaded in engineered exosomes, assuming that an optimized CD8+ T cell immune response would correlate with a more effective depletion of tumor cells in the therapeutic setting. By considering HPV-E6 as a model of TAA, we found that the in vitro co-administration of engineered exosomes and ISCOMATRIXTM adjuvant, i.e., an adjuvant composed of purified ISCOPREPTM saponin, cholesterol, and phospholipids, led to a stronger antigen cross-presentation in both B- lymphoblastoid cell lines ( and monocyte-derived immature dendritic cells compared with that induced by the exosomes alone. Consistently, the co-inoculation in mice of ISCOMATRIXTM adjuvant and engineered exosomes induced a significant increase of TAA-specific CD8+ T cells compared to mice immunized with the exosomes alone. This result holds promise for effective usage of exosomes as well as alternative nanovesicles in anti-tumor therapeutic approaches. |
| first_indexed | 2024-04-12T05:45:47Z |
| format | Article |
| id | doaj.art-e41d71a4424449e0a2283e7ce8a2f867 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-04-12T05:45:47Z |
| publishDate | 2016-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-e41d71a4424449e0a2283e7ce8a2f8672022-12-22T03:45:27ZengMDPI AGVaccines2076-393X2016-11-01444210.3390/vaccines4040042vaccines4040042The CD8+ T Cell-Mediated Immunity Induced by HPV-E6 Uploaded in Engineered Exosomes Is Improved by ISCOMATRIXTM AdjuvantFrancesco Manfredi0Paola di Bonito1Barbara Ridolfi2Simona Anticoli3Claudia Arenaccio4Chiara Chiozzini5Adriana Baz Morelli6Maurizio Federico7National AIDS Center, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, ItalyDepartment of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, ItalyDepartment of Therapeutic Research and Medicine Evaluation, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, ItalyNational AIDS Center, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, ItalyNational AIDS Center, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, ItalyNational AIDS Center, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, ItalyCSL, Ltd., Bio21 Institute, 30 Flemington Road, Melbourne, VIC 3010, AustraliaNational AIDS Center, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, ItalyWe recently described the induction of an efficient CD8+ T cell-mediated immune response against a tumor-associated antigen (TAA) uploaded in engineered exosomes used as an immunogen delivery tool. This immune response cleared tumor cells inoculated after immunization, and controlled the growth of tumors implanted before immunization. We looked for new protocols aimed at increasing the CD8+ T cell specific response to the antigen uploaded in engineered exosomes, assuming that an optimized CD8+ T cell immune response would correlate with a more effective depletion of tumor cells in the therapeutic setting. By considering HPV-E6 as a model of TAA, we found that the in vitro co-administration of engineered exosomes and ISCOMATRIXTM adjuvant, i.e., an adjuvant composed of purified ISCOPREPTM saponin, cholesterol, and phospholipids, led to a stronger antigen cross-presentation in both B- lymphoblastoid cell lines ( and monocyte-derived immature dendritic cells compared with that induced by the exosomes alone. Consistently, the co-inoculation in mice of ISCOMATRIXTM adjuvant and engineered exosomes induced a significant increase of TAA-specific CD8+ T cells compared to mice immunized with the exosomes alone. This result holds promise for effective usage of exosomes as well as alternative nanovesicles in anti-tumor therapeutic approaches.http://www.mdpi.com/2076-393X/4/4/42adjuvantexosomesNefHPV-E6CD8+ T immune response |
| spellingShingle | Francesco Manfredi Paola di Bonito Barbara Ridolfi Simona Anticoli Claudia Arenaccio Chiara Chiozzini Adriana Baz Morelli Maurizio Federico The CD8+ T Cell-Mediated Immunity Induced by HPV-E6 Uploaded in Engineered Exosomes Is Improved by ISCOMATRIXTM Adjuvant Vaccines adjuvant exosomes Nef HPV-E6 CD8+ T immune response |
| title | The CD8+ T Cell-Mediated Immunity Induced by HPV-E6 Uploaded in Engineered Exosomes Is Improved by ISCOMATRIXTM Adjuvant |
| title_full | The CD8+ T Cell-Mediated Immunity Induced by HPV-E6 Uploaded in Engineered Exosomes Is Improved by ISCOMATRIXTM Adjuvant |
| title_fullStr | The CD8+ T Cell-Mediated Immunity Induced by HPV-E6 Uploaded in Engineered Exosomes Is Improved by ISCOMATRIXTM Adjuvant |
| title_full_unstemmed | The CD8+ T Cell-Mediated Immunity Induced by HPV-E6 Uploaded in Engineered Exosomes Is Improved by ISCOMATRIXTM Adjuvant |
| title_short | The CD8+ T Cell-Mediated Immunity Induced by HPV-E6 Uploaded in Engineered Exosomes Is Improved by ISCOMATRIXTM Adjuvant |
| title_sort | cd8 t cell mediated immunity induced by hpv e6 uploaded in engineered exosomes is improved by iscomatrixtm adjuvant |
| topic | adjuvant exosomes Nef HPV-E6 CD8+ T immune response |
| url | http://www.mdpi.com/2076-393X/4/4/42 |
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