Novel therapeutic approach against Epstein-Barr virus-associated tumors – ScienceDaily

EBV infects approximately 95% of the human population and causes more than 200,000 cancer cases each year. Around 2% of all cancer deaths are due to EBV-related malignancies. EBV-associated tumors include Burkitt’s lymphoma, Hodgkin’s lymphoma, nasopharyngeal carcinoma, gastric cancer, and post-transplant lymphoproliferative disease, etc. Current treatments for EBV-associated tumors are limited, with significant out-of-target toxicities and incomplete effectiveness in relapsed or refractory diseases. V? 2-T cells are innate T cells with anti-tumor potentials against EBV-associated tumors. Unfortunately, its clinical translation is limited as it is difficult to identify V? Expand 2 T cells from some cancer patients. Exosomes are small extracellular vesicles made up of endosomes that mediate intercellular communication. Compared to cell-based therapy, cell-free exosomes have advantages with higher safety, easier storage and lower costs. The antitumor activity of exosomes determined by V? 2 T cells (V δ 2 T exos), but remains unknown.

research results

Here, the team found that V & dgr; 2-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 tumor cells via the FasL and TRAIL pathways and promoted EBV antigen-specific CD4 and CD8 T cell expansion. Administration of V & dgr; 2-T-Exos effectively controlled EBV-associated tumors in immunodeficient and humanized mice. Since the expansion of V? 2-T cells and the large-scale production of autologous Vδ2-T exos from cancer patients ex vivo, the team further investigated the antitumor activity of allogeneic Vδ2-T exos in humanized mouse cancer models. Interestingly, the team found that allogeneic Vδ2-T exos had more potent antitumor activity than autologous Vδ2-T exos in humanized mice; The allogeneic Vδ2-T-exos increased the infiltration of T-cells into tumor tissue and induced a more robust CD4- and CD8-T-cell-mediated anti-tumor immunity. Compared to exosomes derived from NK cells with direct cytotoxic antitumor activity or dendritic cells that induced T-cell antitumor responses, Vδ2-T-exos display dual antitumor activities by killing tumor cells directly and inducing T-cell-mediated ones indirectly Anti-tumor responses, resulting in more effective control of EBV-associated tumors.

“Our study provides the first evidence for the anti-tumor activities of Vδ2-T-Exos against EBV-associated tumors. These exosomes could effectively control EBV-associated cancers in several mouse models. More importantly, allogeneic Vδ2-T exos were higher in therapeutic efficacy than autologous Vδ2 T exos. 2-T-Exos for the control of EBV-associated tumors. Therefore, the V & dgr; 2-T-Exos can be used to treat patients with EBV-associated tumors, which is of great advantage for the clinical application of these tumors, “said Professor Tu Wen-wei, Professor of Child Immunology at Antony and Nina Chan, Department of Pediatric and Adolescent Medicine, HKUMed, who led the research.

Importance of the study

The results of the study have significant implications for cancer immunotherapy. First, the identification that Vδ2-T-Exos have potent immunostimulatory property suggests that they could be designed as a cancer vaccine by acting as an immune adjuvant and delivering immunogens. Second, the Vδ2-T-Exos has advantages over other exosome-based therapies (e.g. NK-Exos and DC-Exos) because it has dual anti-tumor activities and is easier to manufacture. Third, the results that allogeneic Vδ2-T exos have higher antitumor efficacy than autologous Vδ2-T exos can greatly improve the clinical feasibility of Vδ2-T exos, since the production of allogeneic exosomes does not require personalized procedures and is easier quality control, Standardization and centralization for clinical use.

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Materials provided by The University of Hong Kong. Note: The content can be edited by style and length.