动物实验,Vδ2-T细胞 z-bo 2020-11-27 336

　　In a new study, researchers from the University of Hong Kong and the University of Science and Technology of China reported that exosomes derived from Vδ2-T cells (hereinafter referred to as Vδ2-T-Exos) can effectively control Epstein-Barr virus ( EBV) related tumors, and induce T cell anti-tumor immune response. These breakthrough new findings for Vδ2-T-Exos provide new insights for the development of new therapies for EBV-related tumors.

　　EBV infects about 95% of the human population, causing more than 200,000 cases of cancer each year, and about 2% of cancer deaths are due to malignant tumors caused by EBV. EBV-related tumors include Burkitt’s lymphoma, Hodgkin’s lymphoma, nasopharyngeal carcinoma, gastric tumors and post-transplant lymphoproliferative diseases.

　　The current treatment options for EBV-related tumors are limited, and there are quite a lot of unwanted off-target toxicity and incomplete curative effect on relapsed or refractory diseases. Vδ2-T cells are similar to congenital T cells and have antitumor potential against EBV-related tumors. Unfortunately, due to the difficulty of expansion of Vδ2-T cells in some cancer patients, their clinical transformation is limited. Exosomes are small extracellular vesicles derived from endosomes that mediate communication between cells. Compared with cell therapy, cell-free exosomes have the advantages of higher safety, easier storage, and lower cost. However, the anti-tumor activity of Vδ2-T-Exos is still unknown.

　　In this new study, these researchers discovered that Vδ2-T-Exos contains death-inducing ligands (FasL and TRAIL) and immunostimulatory molecules (CD80, CD86, MHC-I and MHC-II). Vδ2-T-Exos targets and effectively kills EBV-related tumor cells through FasL and TRAIL pathways, and promotes the expansion of EBV antigen-specific CD4 T cells and CD8 T cells. Administration of Vδ2-T-Exos can effectively control EBV-related tumors in immunodeficient mice and humanized mice.

　　Due to the challenges of large-scale expansion of Vδ2-T cells in vitro and large-scale preparation of autologous Vδ2-T-Exos from cancer patients, these researchers further explored the role of allogeneic Vδ2-T-Exos in humanized mouse cancer models The anti-tumor activity. Interestingly, they found that in humanized mice, allogeneic Vδ2-T-Exos had more effective anti-tumor activity than autologous Vδ2-T-Exos; allogeneic Vδ2-T-Exos increased the T cell’s effect on tumor tissues. Infiltrate and induce a more powerful anti-tumor immune response mediated by CD4 T cells and CD8 T cells. It is similar to exosomes produced by NK cells with direct cytotoxic anti-tumor activity (hereinafter referred to as NK-Exos) or exosomes produced by dendritic cells that can induce T cell anti-tumor response (hereinafter referred to as DC-Exos) Compared with, Vδ2-T-Exos has dual anti-tumor activity of directly killing tumor cells and indirectly inducing T cell-mediated anti-tumor response, thus more effectively controlling EBV-related tumors.

　　Corresponding author of the paper, Dr. Wenwei Tu, Professor of Pediatric Immunology, Department of Child and Adolescent Medicine, University of Hong Kong, Li Ka Shing School of Medicine, The University of Hong Kong, said, "Our study provides the first evidence for the anti-tumor activity of Vδ2-T-Exos on EBV-related tumors. These exosomes can effectively control EBV-related cancers in a variety of mouse models. More importantly, allogeneic Vδ2-T-Exos has a higher therapeutic effect in controlling EBV-related tumors than autologous Vδ2-T-Exos. Therefore. , Vδ2-T-Exos prepared from healthy donors may be used to treat patients with EBV-related tumors, which is very beneficial to the clinical application of this new method."

　　These research results have important implications for cancer immunotherapy. First of all, Vδ2-T-Exos has powerful immunostimulatory properties, which suggests that it may be designed as a cancer vaccine, acting as an immune adjuvant and delivering immunogens. Second, Vδ2-T-Exos has advantages over other exosome therapies (such as NK-Exos and DC-Exos), shows dual anti-tumor activity, and is easier to prepare. Third, allogeneic Vδ2-T-Exos has higher anti-tumor efficacy than autologous Vδ2-T-Exos, which can greatly improve the clinical feasibility of Vδ2-T-Exos, because the preparation of allogeneic exosomes does not require Individualized procedures are more convenient for clinical application in terms of quality control, standardization and centralization.