Systemically targeted cancer immunotherapy and gene delivery using transmorphic particles
Issued Date
2022-08-08
Resource Type
ISSN
17574676
eISSN
17574684
Scopus ID
2-s2.0-85132745584
Pubmed ID
35758207
Journal Title
EMBO Molecular Medicine
Volume
14
Issue
8
Rights Holder(s)
SCOPUS
Bibliographic Citation
EMBO Molecular Medicine Vol.14 No.8 (2022)
Suggested Citation
Asavarut P., Waramit S., Suwan K., Marais G.J.K., Chongchai A., Benjathummarak S., Al-Bahrani M., Vila-Gomez P., Williams M., Kongtawelert P., Yata T., Hajitou A. Systemically targeted cancer immunotherapy and gene delivery using transmorphic particles. EMBO Molecular Medicine Vol.14 No.8 (2022). doi:10.15252/emmm.202115418 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/83636
Title
Systemically targeted cancer immunotherapy and gene delivery using transmorphic particles
Other Contributor(s)
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 (TNF (Formula presented.)) 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.