In Vivo Evaluation of a New Recombinant Hyaluronidase to Improve Gene Electro-Transfer Protocols for DNA-Based Drug Delivery against Cancer
Cancer vaccines based on plasmid DNA represent a good therapeutic perspective, despite their low potency. Animal-derived hyaluronidases (Hyals) are employed in oncological clinical practice. Hyal has been also demonstrated to be a good enhancer of intramuscular Gene Electro-Transfer (GET) efficiency...
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| Format: | Article |
| Language: | English |
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MDPI AG
2018-10-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/10/11/405 |
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| author | Mariangela De Robertis Lise Pasquet Luisa Loiacono Elisabeth Bellard Luciano Messina Susanna Vaccaro Roberta Di Pasquale Vito Michele Fazio Marie-Pierre Rols Justin Teissie Muriel Golzio Emanuela Signori |
| author_facet | Mariangela De Robertis Lise Pasquet Luisa Loiacono Elisabeth Bellard Luciano Messina Susanna Vaccaro Roberta Di Pasquale Vito Michele Fazio Marie-Pierre Rols Justin Teissie Muriel Golzio Emanuela Signori |
| author_sort | Mariangela De Robertis |
| collection | DOAJ |
| description | Cancer vaccines based on plasmid DNA represent a good therapeutic perspective, despite their low potency. Animal-derived hyaluronidases (Hyals) are employed in oncological clinical practice. Hyal has been also demonstrated to be a good enhancer of intramuscular Gene Electro-Transfer (GET) efficiency in anti-cancer preclinical protocols, with increased transfected cells and higher expression of the encoded genes. Nevertheless, the use of animal-derived Hyals results limited respect to their potentialities, since such preparations could be affected by low purity, variable potency and uncertain safety. To improve the delivery of intramuscular GET-based protocols in mouse, we investigated a new recombinant Hyal, the rHyal-<i>sk</i>, to assess in vivo safety and activity of this treatment at cellular and biochemical levels. We evaluated the cellular events and the inflammation chemical mediators involved at different time points after rHyal-<i>sk</i> administration plus GET. Our results demonstrated the in vivo safety and efficacy of rHyal-<i>sk</i> when injected once intramuscularly in association with GET, with no toxicity, good plasmid in-take ability, useful inflammatory response activation, and low immunogenicity. Following these findings, we would recommend the use of the new rHyal-<i>sk</i> for the delivery of DNA-based vaccines and immunotherapy, as well as into clinical practice, for tumor disease treatments. |
| first_indexed | 2024-03-12T06:15:18Z |
| format | Article |
| id | doaj.art-07c1ca08a3384b82beee66eb2ea34475 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T06:15:18Z |
| publishDate | 2018-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-07c1ca08a3384b82beee66eb2ea344752023-09-03T02:38:58ZengMDPI AGCancers2072-66942018-10-01101140510.3390/cancers10110405cancers10110405In Vivo Evaluation of a New Recombinant Hyaluronidase to Improve Gene Electro-Transfer Protocols for DNA-Based Drug Delivery against CancerMariangela De Robertis0Lise Pasquet1Luisa Loiacono2Elisabeth Bellard3Luciano Messina4Susanna Vaccaro5Roberta Di Pasquale6Vito Michele Fazio7Marie-Pierre Rols8Justin Teissie9Muriel Golzio10Emanuela Signori11Department of Biosciences, Biotechnology and Biopharmaceutics, University of Bari “A. Moro”, via Orabona 4, 70126 Bari, ItalyVaccine Branch, CCR, NCI, NIH, Bethesda, MD 20892, USALaboratory of Molecular Medicine and Biotechnology, University Campus Bio-Medico of Rome, via Alvaro del Portillo 21, 00128 Rome, ItalyInstitut de Pharmacologie et Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, BP64182, 205 Route de Narbonne, 31077 Toulouse, FranceFidia Farmaceutici S.p.A., Local Unit Fidia Research Sud, Contrada Pizzuta snc, 96017 Noto, Siracusa, ItalyFidia Farmaceutici S.p.A., Local Unit Fidia Research Sud, Contrada Pizzuta snc, 96017 Noto, Siracusa, ItalyFidia Farmaceutici S.p.A., Local Unit Fidia Research Sud, Contrada Pizzuta snc, 96017 Noto, Siracusa, ItalyLaboratory of Molecular Medicine and Biotechnology, University Campus Bio-Medico of Rome, via Alvaro del Portillo 21, 00128 Rome, ItalyInstitut de Pharmacologie et Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, BP64182, 205 Route de Narbonne, 31077 Toulouse, FranceInstitut de Pharmacologie et Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, BP64182, 205 Route de Narbonne, 31077 Toulouse, FranceInstitut de Pharmacologie et Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, BP64182, 205 Route de Narbonne, 31077 Toulouse, FranceLaboratory of Molecular Medicine and Biotechnology, University Campus Bio-Medico of Rome, via Alvaro del Portillo 21, 00128 Rome, ItalyCancer vaccines based on plasmid DNA represent a good therapeutic perspective, despite their low potency. Animal-derived hyaluronidases (Hyals) are employed in oncological clinical practice. Hyal has been also demonstrated to be a good enhancer of intramuscular Gene Electro-Transfer (GET) efficiency in anti-cancer preclinical protocols, with increased transfected cells and higher expression of the encoded genes. Nevertheless, the use of animal-derived Hyals results limited respect to their potentialities, since such preparations could be affected by low purity, variable potency and uncertain safety. To improve the delivery of intramuscular GET-based protocols in mouse, we investigated a new recombinant Hyal, the rHyal-<i>sk</i>, to assess in vivo safety and activity of this treatment at cellular and biochemical levels. We evaluated the cellular events and the inflammation chemical mediators involved at different time points after rHyal-<i>sk</i> administration plus GET. Our results demonstrated the in vivo safety and efficacy of rHyal-<i>sk</i> when injected once intramuscularly in association with GET, with no toxicity, good plasmid in-take ability, useful inflammatory response activation, and low immunogenicity. Following these findings, we would recommend the use of the new rHyal-<i>sk</i> for the delivery of DNA-based vaccines and immunotherapy, as well as into clinical practice, for tumor disease treatments.https://www.mdpi.com/2072-6694/10/11/405DNA-based drug deliveryhyaluronidasegene electro-transferDNA vaccinationcancer therapyoncoimmunologytranslational protocols |
| spellingShingle | Mariangela De Robertis Lise Pasquet Luisa Loiacono Elisabeth Bellard Luciano Messina Susanna Vaccaro Roberta Di Pasquale Vito Michele Fazio Marie-Pierre Rols Justin Teissie Muriel Golzio Emanuela Signori In Vivo Evaluation of a New Recombinant Hyaluronidase to Improve Gene Electro-Transfer Protocols for DNA-Based Drug Delivery against Cancer Cancers DNA-based drug delivery hyaluronidase gene electro-transfer DNA vaccination cancer therapy oncoimmunology translational protocols |
| title | In Vivo Evaluation of a New Recombinant Hyaluronidase to Improve Gene Electro-Transfer Protocols for DNA-Based Drug Delivery against Cancer |
| title_full | In Vivo Evaluation of a New Recombinant Hyaluronidase to Improve Gene Electro-Transfer Protocols for DNA-Based Drug Delivery against Cancer |
| title_fullStr | In Vivo Evaluation of a New Recombinant Hyaluronidase to Improve Gene Electro-Transfer Protocols for DNA-Based Drug Delivery against Cancer |
| title_full_unstemmed | In Vivo Evaluation of a New Recombinant Hyaluronidase to Improve Gene Electro-Transfer Protocols for DNA-Based Drug Delivery against Cancer |
| title_short | In Vivo Evaluation of a New Recombinant Hyaluronidase to Improve Gene Electro-Transfer Protocols for DNA-Based Drug Delivery against Cancer |
| title_sort | in vivo evaluation of a new recombinant hyaluronidase to improve gene electro transfer protocols for dna based drug delivery against cancer |
| topic | DNA-based drug delivery hyaluronidase gene electro-transfer DNA vaccination cancer therapy oncoimmunology translational protocols |
| url | https://www.mdpi.com/2072-6694/10/11/405 |
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