A analysis staff at LKS School of Drugs, The College of Hong Kong (HKUMed) found that exosomes derived from V?2-T cells (Vδ2-T-Exos) can successfully management Epstein-Barr virus-associated tumours and induce T-cell anti-tumour immunity. The novel findings of Vδ2-T-Exos present insights into new therapeutic method for Epstein-Barr virus (EBV)-associated tumours. The bottom-breaking findings have been revealed within the main tutorial journal, Science Translational Drugs.
EBV infects about 95% of the human inhabitants and causes greater than 200,000 instances of most cancers annually and that round 2% of all most cancers deaths are on account of EBV-attributable malignancies. EBV-associated tumours embody Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma, gastric tumour and post-transplant lymphoproliferative illness, and many others. Present remedy choices for EBV-associated tumours are restricted with significantly undesirable off-target toxicities and incomplete effectiveness for relapsed or refractory illness. V?2-T cells are innate-like T cells with anti-tumour potentials towards EBV-associated tumours. Sadly, its medical translation is restricted as a result of V?2-T cells from some most cancers sufferers are troublesome to be expanded. Exosomes are endosome-originated small extracellular vesicles that mediate intercellular communication. In contrast with cell-based remedy, cell-free exosomes have benefits with greater security, simpler storage, and decrease prices. Nonetheless, the anti-tumour exercise of exosomes derived from V?2-T cells (Vδ2-T-Exos) stays unknown.
Herein, the staff discovered that Vδ2-T-Exos contained death-inducing ligands (FasL and TRAIL) and immunostimulatory molecules (CD80, CD86, MHC class I and II). Vδ2-T-Exos focused and effectively killed EBV-associated tumour cells by way of FasL and TRAIL pathways and promoted EBV antigen-specific CD4 and CD8 T cell growth. Administration of Vδ2-T-Exos successfully managed EBV-associated tumours in immunodeficient and humanized mice. As a result of increasing V?2-T cells and making ready autologous Vδ2-T-Exos from most cancers sufferers ex vivo in giant scale is difficult, the staff additional explored the anti-tumour exercise of allogeneic Vδ2-T-Exos in humanized mouse most cancers fashions. Apparently, the staff discovered that allogeneic Vδ2-T-Exos had more practical anti-tumour exercise than autologous Vδ2-T-Exos in humanized mice; the allogeneic Vδ2-T-Exos elevated the infiltration of T cells into tumour tissues and induced extra sturdy CD4 and CD8 T cells-mediated anti-tumour immunity. In contrast with exosomes derived from NK cells with direct cytotoxic anti-tumour exercise or dendritic cells that induced T-cell anti-tumour responses, Vδ2-T-Exos have twin anti-tumour actions by straight killing tumour cells and not directly inducing T cells-mediated anti-tumour responses, thus leading to more practical management of EBV-associated tumours.
“Our research gives the primary proof in regards to the anti-tumour actions of Vδ2-T-Exos towards EBV-associated tumours. These exosomes may successfully management EBV-associated cancers in a number of mouse fashions. Extra importantly, allogeneic Vδ2-T-Exos had greater therapeutic efficacy than autologous Vδ2-T-Exos to manage EBV-associated tumours. Due to this fact, the Vδ2-T-Exos ready from wholesome donors can be utilized to deal with sufferers with EBV-associated tumours, which is very helpful to the medical utility of this novel method,” mentioned Professor Tu Wen-wei, Antony and Nina Chan professor in Paediatric Immunology, Division of Paediatrics and Adolescent Drugs, HKUMed, who led the analysis.
Significance of the research
The findings of the research have important implications in most cancers immunotherapy. Firstly, the identification that Vδ2-T-Exos has potent immunostimulatory property means that they might be designed as a most cancers vaccine by serving as immune adjuvant and delivering immunogens. Secondly, the Vδ2-T-Exos has benefits over different exosome-based therapies (e.g. NK-Exos and DC-Exos) by displaying twin anti-tumour actions and are simpler in preparation. Thirdly, the outcomes that allogeneic Vδ2-T-Exos have greater anti-tumour efficacies than autologous Vδ2-T-Exos can enormously improve the medical feasibility of Vδ2-T-Exos, as a result of the preparation of allogeneic exosomes doesn’t require personalised procedures and is less complicated in high quality management, standardization and centralization for medical utility.