Novel therapeutic approach against Epstein-Barr virus-associated tumors — ScienceDaily
A research team at LKS Faculty of Medicine, The University of Hong Kong (HKUMed) discovered that exosomes derived from V?2-T cells (Vδ2-T-Exos) can effectively control Epstein-Barr virus-associated tumours and induce T-cell anti-tumour immunity. The novel findings of Vδ2-T-Exos provide insights into new therapeutic approach for Epstein-Barr virus (EBV)-associated tumours. The ground-breaking findings have been published in the leading academic journal, Science Translational Medicine.
EBV infects about 95% of the human population and causes more than 200,000 cases of cancer each year and that around 2% of all cancer deaths are due to EBV-attributable malignancies. EBV-associated tumours include Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma, gastric tumour and post-transplant lymphoproliferative disease, etc. Current treatment options for EBV-associated tumours are limited with considerably unwanted off-target toxicities and incomplete effectiveness for relapsed or refractory disease. V?2-T cells are innate-like T cells with anti-tumour potentials against EBV-associated tumours. Unfortunately, its clinical translation is limited because V?2-T cells from some cancer patients are difficult to be expanded. Exosomes are endosome-originated small extracellular vesicles that mediate intercellular communication. Compared with cell-based therapy, cell-free exosomes have advantages with higher safety, easier storage, and lower costs. However, the anti-tumour activity of exosomes derived from V?2-T cells (Vδ2-T-Exos) remains unknown.
Herein, the team found that Vδ2-T-Exos contained death-inducing ligands (FasL and TRAIL) and immunostimulatory molecules (CD80, CD86, MHC class I and II). Vδ2-T-Exos targeted and efficiently killed EBV-associated tumour cells through FasL and TRAIL pathways and promoted EBV antigen-specific CD4 and CD8 T cell expansion. Administration of Vδ2-T-Exos effectively controlled EBV-associated tumours in immunodeficient and humanized mice. Because expanding V?2-T cells and preparing autologous Vδ2-T-Exos from cancer patients ex vivo in large scale is challenging, the team further explored the anti-tumour activity of allogeneic Vδ2-T-Exos in humanized mouse cancer models. Interestingly, the team found that allogeneic Vδ2-T-Exos