{Reference Type}: Journal Article
{Title}: Systemically targeted cancer immunotherapy and gene delivery using transmorphic particles.
{Author}: Asavarut P;Waramit S;Suwan K;Marais GJK;Chongchai A;Benjathummarak S;Al-Bahrani M;Vila-Gomez P;Williams M;Kongtawelert P;Yata T;Hajitou A;
{Journal}: EMBO Mol Med
{Volume}: 14
{Issue}: 8
{Year}: 08 2022 8
{Factor}: 14.26
{DOI}: 10.15252/emmm.202115418
{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.