Systemically targeted cancer immunotherapy and gene delivery using transmorphic particles.
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 Information
Paladd Asavarut: Cancer Phagotherapy, Department of Brain Sciences, Imperial College London, London, UK.
Sajee Waramit: Cancer Phagotherapy, Department of Brain Sciences, Imperial College London, London, UK.
Keittisak Suwan: Cancer Phagotherapy, Department of Brain Sciences, Imperial College London, London, UK. ORCID
Gert J K Marais: Cancer Phagotherapy, Department of Brain Sciences, Imperial College London, London, UK.
Aitthiphon Chongchai: Cancer Phagotherapy, Department of Brain Sciences, Imperial College London, London, UK. ORCID
Surachet Benjathummarak: Cancer Phagotherapy, Department of Brain Sciences, Imperial College London, London, UK. ORCID
Mariam Al-Bahrani: Cancer Phagotherapy, Department of Brain Sciences, Imperial College London, London, UK.
Paula Vila-Gomez: Cancer Phagotherapy, Department of Brain Sciences, Imperial College London, London, UK. ORCID
Matthew Williams: Department of Surgery and Cancer, Imperial College London, London, UK.
Prachya Kongtawelert: Thailand Excellence Centre for Tissue Engineering and Stem Cells, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Teerapong Yata: Cancer Phagotherapy, Department of Brain Sciences, Imperial College London, London, UK.
Amin Hajitou: Cancer Phagotherapy, Department of Brain Sciences, Imperial College London, London, UK. ORCID
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 (TNF ) 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.
