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 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 α ) 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.

• Authors: 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
• Journal: EMBO molecular medicine (EMBO Mol Med) Vol. 14 Issue 8 Pg. e15418 (08 08 2022) ISSN: 1757-4684 [Electronic] England
• PMID: 35758207 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 The Authors. Published under the terms of the CC BY 4.0 license.

Chemical References

• Cytokines

Topics

• Bacteriophages (genetics)
• Cytokines (metabolism)
• Dependovirus (genetics)
• Gene Transfer Techniques
• Genetic Vectors
• Humans
• Immunotherapy
• Neoplasms (genetics, therapy)
• Transgenes