Trojan-horse silk fibroin nanocarriers loaded with a re-call antigen to redirect immunity against cancer
Background The current challenge for immunotherapies is to generate effective antitumor immunity. Since tumor immune escape mechanisms do not impact pre-existing and consolidated immune responses, we tested the hypothesis of redirecting a pregenerated immunity to cancer: to recall a non-tumor antige...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2023-01-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/11/1/e005916.full |
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| author | Luca Mastracci Patrizio Castagnola Elia Bari Francesca Ferrera Tiziana Altosole Sara Perteghella Pierluigi Mauri Rossana Rossi Giulia Passignani Martina Galati Giuseppina Iliana Astone Maddalena Mastrogiacomo Daniela Fenoglio Dario Di Silvestre Maria Luisa Torre Gilberto Filaci |
| author_facet | Luca Mastracci Patrizio Castagnola Elia Bari Francesca Ferrera Tiziana Altosole Sara Perteghella Pierluigi Mauri Rossana Rossi Giulia Passignani Martina Galati Giuseppina Iliana Astone Maddalena Mastrogiacomo Daniela Fenoglio Dario Di Silvestre Maria Luisa Torre Gilberto Filaci |
| author_sort | Luca Mastracci |
| collection | DOAJ |
| description | Background The current challenge for immunotherapies is to generate effective antitumor immunity. Since tumor immune escape mechanisms do not impact pre-existing and consolidated immune responses, we tested the hypothesis of redirecting a pregenerated immunity to cancer: to recall a non-tumor antigen response against the tumor, silk fibroin nanoparticles (SFNs) have been selected as ‘Trojan-horse’ carriers, promoting the antigen uptake by the tumor cells.Methods SFNs have been loaded with either ovalbumin (OVA) or CpG oligonucleotide (CpG) as antigen or adjuvant, respectively. In vitro uptake of SFNs by tumor (B16/F10 melanoma and MB49 bladder cancer) or dendritic cells, as well as the presence of OVA-specific T cells in splenic and tumor-infiltrating lymphocytes, were assessed by cytometric analyses. Proof-of-concept of in vivo efficacy was achieved in an OVA-hyperimmune B16/F10 murine melanoma model: SFNs-OVA or SFNs-CpG were injected, separately or in association, into the subcutaneous peritumoral area. Cancer dimensions/survival time were monitored, while, at the molecular level, system biology approaches based on graph theory and experimental proteomic data were performed.Results SFNs were efficiently in vitro uptaken by cancer and dendritic cells. In vivo peritumor administration of SFNs-OVA redirected OVA-specific cytotoxic T cells intratumorally. Proteomics and systems biology showed that peritumoral treatment with either SFNs-OVA or SFNs-CpG dramatically modified tumor microenvironment with respect to the control (CTR), mainly involving functional modules and hubs related to angiogenesis, inflammatory mediators, immune function, T complex and serpins expression, redox homeostasis, and energetic metabolism. Both SFNs-OVA and SFNs-CpG significantly delayed melanoma growth/survival time, and their effect was additive.Conclusions Both SFNs-OVA and SFNs-CpG induce effective anticancer response through complementary mechanisms and show the efficacy of an innovative active immunotherapy approach based on the redirection of pre-existing immunity against cancer cells. This approach could be universally applied for solid cancer treatments if translated into the clinic using re-call antigens of childhood vaccination. |
| format | Article |
| id | doaj-art-7278e45965df45a3b51cb261e7420bb6 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-7278e45965df45a3b51cb261e7420bb62025-01-29T11:10:09ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262023-01-0111110.1136/jitc-2022-005916Trojan-horse silk fibroin nanocarriers loaded with a re-call antigen to redirect immunity against cancerLuca Mastracci0Patrizio Castagnola1Elia Bari2Francesca Ferrera3Tiziana Altosole4Sara Perteghella5Pierluigi Mauri6Rossana Rossi7Giulia Passignani8Martina Galati9Giuseppina Iliana Astone10Maddalena Mastrogiacomo11Daniela Fenoglio12Dario Di Silvestre13Maria Luisa Torre14Gilberto Filaci15Anatomic Pathology, Department of Surgical Sciences and Integrated Diagnostics (DISC), Univeristy of Genova, Genova, ItalyBiotherapy Unit, IRCCS Ospedale Policlinico San Martino, Genova, Liguria, ItalyDepartment of Pharmaceutical Sciences, University of Piemonte Orientale, Novara, Piemonte, ItalyDepartment of Internal Medicine and Centre of Excellence for Biomedical Research, University of Genoa, Genova, Liguria, ItalyDepartment of Internal Medicine and Centre of Excellence for Biomedical Research, University of Genoa, Genova, Liguria, ItalyDepartment of Drug Sciences, University of Pavia, Pavia, Lombardia, ItalyInstitute for Biomedical Technologies, ITB CNR, Segrate, Lombardia, ItalyInstitute for Biomedical Technologies, ITB CNR, Segrate, Lombardia, ItalyInstitute for Biomedical Technologies, ITB CNR, Segrate, Lombardia, ItalyDepartment of Internal Medicine and Centre of Excellence for Biomedical Research, University of Genoa, Genova, Liguria, ItalyDepartment of Internal Medicine and Centre of Excellence for Biomedical Research, University of Genoa, Genova, Liguria, ItalyDepartment of Internal Medicine and Centre of Excellence for Biomedical Research, University of Genoa, Genova, Liguria, Italy4Università di Genova, Center of Excellence for Biomedical Research, Genova, ItalyInstitute for Biomedical Technologies, ITB CNR, Segrate, Lombardia, ItalyDepartment of Pharmaceutical Sciences, University of Piemonte Orientale, Novara, Piemonte, Italy4Università di Genova, Center of Excellence for Biomedical Research, Genova, ItalyBackground The current challenge for immunotherapies is to generate effective antitumor immunity. Since tumor immune escape mechanisms do not impact pre-existing and consolidated immune responses, we tested the hypothesis of redirecting a pregenerated immunity to cancer: to recall a non-tumor antigen response against the tumor, silk fibroin nanoparticles (SFNs) have been selected as ‘Trojan-horse’ carriers, promoting the antigen uptake by the tumor cells.Methods SFNs have been loaded with either ovalbumin (OVA) or CpG oligonucleotide (CpG) as antigen or adjuvant, respectively. In vitro uptake of SFNs by tumor (B16/F10 melanoma and MB49 bladder cancer) or dendritic cells, as well as the presence of OVA-specific T cells in splenic and tumor-infiltrating lymphocytes, were assessed by cytometric analyses. Proof-of-concept of in vivo efficacy was achieved in an OVA-hyperimmune B16/F10 murine melanoma model: SFNs-OVA or SFNs-CpG were injected, separately or in association, into the subcutaneous peritumoral area. Cancer dimensions/survival time were monitored, while, at the molecular level, system biology approaches based on graph theory and experimental proteomic data were performed.Results SFNs were efficiently in vitro uptaken by cancer and dendritic cells. In vivo peritumor administration of SFNs-OVA redirected OVA-specific cytotoxic T cells intratumorally. Proteomics and systems biology showed that peritumoral treatment with either SFNs-OVA or SFNs-CpG dramatically modified tumor microenvironment with respect to the control (CTR), mainly involving functional modules and hubs related to angiogenesis, inflammatory mediators, immune function, T complex and serpins expression, redox homeostasis, and energetic metabolism. Both SFNs-OVA and SFNs-CpG significantly delayed melanoma growth/survival time, and their effect was additive.Conclusions Both SFNs-OVA and SFNs-CpG induce effective anticancer response through complementary mechanisms and show the efficacy of an innovative active immunotherapy approach based on the redirection of pre-existing immunity against cancer cells. This approach could be universally applied for solid cancer treatments if translated into the clinic using re-call antigens of childhood vaccination.https://jitc.bmj.com/content/11/1/e005916.full |
| spellingShingle | Luca Mastracci Patrizio Castagnola Elia Bari Francesca Ferrera Tiziana Altosole Sara Perteghella Pierluigi Mauri Rossana Rossi Giulia Passignani Martina Galati Giuseppina Iliana Astone Maddalena Mastrogiacomo Daniela Fenoglio Dario Di Silvestre Maria Luisa Torre Gilberto Filaci Trojan-horse silk fibroin nanocarriers loaded with a re-call antigen to redirect immunity against cancer Journal for ImmunoTherapy of Cancer |
| title | Trojan-horse silk fibroin nanocarriers loaded with a re-call antigen to redirect immunity against cancer |
| title_full | Trojan-horse silk fibroin nanocarriers loaded with a re-call antigen to redirect immunity against cancer |
| title_fullStr | Trojan-horse silk fibroin nanocarriers loaded with a re-call antigen to redirect immunity against cancer |
| title_full_unstemmed | Trojan-horse silk fibroin nanocarriers loaded with a re-call antigen to redirect immunity against cancer |
| title_short | Trojan-horse silk fibroin nanocarriers loaded with a re-call antigen to redirect immunity against cancer |
| title_sort | trojan horse silk fibroin nanocarriers loaded with a re call antigen to redirect immunity against cancer |
| url | https://jitc.bmj.com/content/11/1/e005916.full |
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