Systemically targeted cancer immunotherapy and gene delivery using transmorphic particles
Abstract Immunotherapy is a powerful tool for cancer treatment, but the pleiotropic nature of cytokines and immunological agents strongly limits clinical translation and safety. To address this unmet need, we designed and characterised a systemically targeted cytokine gene delivery system through tr...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2022-08-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.202115418 |
| _version_ | 1797280978372132864 |
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| author | Paladd Asavarut Sajee Waramit Keittisak Suwan Gert J K Marais Aitthiphon Chongchai Surachet Benjathummarak Mariam Al‐Bahrani Paula Vila‐Gomez Matthew Williams Prachya Kongtawelert Teerapong Yata Amin Hajitou |
| author_facet | Paladd Asavarut Sajee Waramit Keittisak Suwan Gert J K Marais Aitthiphon Chongchai Surachet Benjathummarak Mariam Al‐Bahrani Paula Vila‐Gomez Matthew Williams Prachya Kongtawelert Teerapong Yata Amin Hajitou |
| author_sort | Paladd Asavarut |
| collection | DOAJ |
| description | Abstract Immunotherapy is a powerful tool for cancer treatment, but the pleiotropic nature of cytokines and immunological agents strongly limits clinical translation and safety. To address this unmet need, we designed and characterised a systemically targeted cytokine gene delivery system through transmorphic encapsidation of human recombinant adeno‐associated virus DNA using coat proteins from a tumour‐targeted bacteriophage (phage). We show that Transmorphic Phage/AAV (TPA) particles provide superior delivery of transgenes over current phage‐derived vectors through greater diffusion across the extracellular space and improved intracellular trafficking. We used TPA to target the delivery of cytokine‐encoding transgenes for interleukin‐12 (IL12), and novel isoforms of IL15 and tumour necrosis factor alpha (TNFα) for tumour immunotherapy. Our results demonstrate selective and efficient gene delivery and immunotherapy against solid tumours in vivo, without harming healthy organs. Our transmorphic particle system provides a promising modality for safe and effective gene delivery, and cancer immunotherapies through cross‐species complementation of two commonly used viruses. |
| first_indexed | 2024-03-07T16:48:56Z |
| format | Article |
| id | doaj.art-30bde55e09624420a5e89b2c824d13d8 |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2024-03-07T16:48:56Z |
| publishDate | 2022-08-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj.art-30bde55e09624420a5e89b2c824d13d82024-03-03T05:42:00ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842022-08-01148n/an/a10.15252/emmm.202115418Systemically targeted cancer immunotherapy and gene delivery using transmorphic particlesPaladd Asavarut0Sajee Waramit1Keittisak Suwan2Gert J K Marais3Aitthiphon Chongchai4Surachet Benjathummarak5Mariam Al‐Bahrani6Paula Vila‐Gomez7Matthew Williams8Prachya Kongtawelert9Teerapong Yata10Amin Hajitou11Cancer Phagotherapy, Department of Brain Sciences Imperial College London London UKCancer Phagotherapy, Department of Brain Sciences Imperial College London London UKCancer Phagotherapy, Department of Brain Sciences Imperial College London London UKCancer Phagotherapy, Department of Brain Sciences Imperial College London London UKCancer Phagotherapy, Department of Brain Sciences Imperial College London London UKCancer Phagotherapy, Department of Brain Sciences Imperial College London London UKCancer Phagotherapy, Department of Brain Sciences Imperial College London London UKCancer Phagotherapy, Department of Brain Sciences Imperial College London London UKDepartment of Surgery and Cancer Imperial College London London UKThailand Excellence Centre for Tissue Engineering and Stem Cells, Faculty of Medicine Chiang Mai University Chiang Mai ThailandCancer Phagotherapy, Department of Brain Sciences Imperial College London London UKCancer Phagotherapy, Department of Brain Sciences Imperial College London London UKAbstract Immunotherapy is a powerful tool for cancer treatment, but the pleiotropic nature of cytokines and immunological agents strongly limits clinical translation and safety. To address this unmet need, we designed and characterised a systemically targeted cytokine gene delivery system through transmorphic encapsidation of human recombinant adeno‐associated virus DNA using coat proteins from a tumour‐targeted bacteriophage (phage). We show that Transmorphic Phage/AAV (TPA) particles provide superior delivery of transgenes over current phage‐derived vectors through greater diffusion across the extracellular space and improved intracellular trafficking. We used TPA to target the delivery of cytokine‐encoding transgenes for interleukin‐12 (IL12), and novel isoforms of IL15 and tumour necrosis factor alpha (TNFα) for tumour immunotherapy. Our results demonstrate selective and efficient gene delivery and immunotherapy against solid tumours in vivo, without harming healthy organs. Our transmorphic particle system provides a promising modality for safe and effective gene delivery, and cancer immunotherapies through cross‐species complementation of two commonly used viruses.https://doi.org/10.15252/emmm.202115418cancer immunotherapycytokinestargeted gene deliveryvector developmentbacteriophage |
| spellingShingle | Paladd Asavarut Sajee Waramit Keittisak Suwan Gert J K Marais Aitthiphon Chongchai Surachet Benjathummarak Mariam Al‐Bahrani Paula Vila‐Gomez Matthew Williams Prachya Kongtawelert Teerapong Yata Amin Hajitou Systemically targeted cancer immunotherapy and gene delivery using transmorphic particles EMBO Molecular Medicine cancer immunotherapy cytokines targeted gene delivery vector development bacteriophage |
| title | Systemically targeted cancer immunotherapy and gene delivery using transmorphic particles |
| title_full | Systemically targeted cancer immunotherapy and gene delivery using transmorphic particles |
| title_fullStr | Systemically targeted cancer immunotherapy and gene delivery using transmorphic particles |
| title_full_unstemmed | Systemically targeted cancer immunotherapy and gene delivery using transmorphic particles |
| title_short | Systemically targeted cancer immunotherapy and gene delivery using transmorphic particles |
| title_sort | systemically targeted cancer immunotherapy and gene delivery using transmorphic particles |
| topic | cancer immunotherapy cytokines targeted gene delivery vector development bacteriophage |
| url | https://doi.org/10.15252/emmm.202115418 |
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