【Animal modeling】-Preclinical animal experiments show that exosomes derived from Vδ2-T cells can effectively control EBV-related tumors and induce T cell anti-tumor immune responses

  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).

   induces the anti-tumor immune response of related tumors and T cells. These groundbreaking new discoveries about Vδ2-T-Exos provide new insights for the development of new therapies for EBV-related tumors. Every year, EBV infects approximately 95% of the population and causes more than 200,000 cases of cancer. About 2% of cancer deaths are due to malignant tumors caused by EBV. Tumors associated with EBV include Burkitt’s lymphoma, Hodgkin’s lymphoma, nasopharyngeal carcinoma, gastric tumors, and post-transplant lymphoproliferative diseases. Current treatment options for EBV-related tumors are limited, with many unwanted off-target toxicities and incomplete treatment for relapsed or refractory diseases. Vδ2-T cells are similar to congenital T cells and have anti-tumor potential against EBV-related tumors. Unfortunately, due to the difficulty in proliferating Vδ2-T cells in some cancer patients, 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 advantage of being safer, easier to store 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 proliferation of EBV antigen-specific CD4T and CD8T cells. Administration of Vδ2-T-Exos can effectively control EBV-related tumors in immunodeficiency and humanized mice. Due to the challenges of large-scale proliferation of Vδ2-T cells in vitro and large-scale preparation of autologous Vδ2-T-Exos from cancer patients, these researchers discovered allogeneic Vδ2-T in humanized mice. Become the role of Exos. Cancer anti-tumor activity in the model. Interestingly, they found that allogeneic Vδ2-T-Exos has more effective anti-tumor activity than autologous Vδ2-T-Exos in humanized mice; allogeneic Vδ2-T-Exos enhances the effect of T cells on tumors. The role of the organization. Strong anti-tumor immune response mediated by CD4T cells and CD8T cells. It is 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 responses (hereinafter referred to as NK-Exos). -Exos). Called DC-Exos). On the contrary, Vδ2-T-Exos has dual anti-tumor activity, which can directly kill tumor cells and indirectly induce T cell-mediated anti-tumor response, thereby making EBV-related tumors more effective. The corresponding author of the paper, Dr. Wenwei Tu, is a professor of pediatric immunology at the Li Ka-shing School of Medicine and Department of Adolescent Medicine at the University of Hong Kong. He said: Vδ2-T-Exos has anti-tumor activity against EBV-related tumors. These exosomes can effectively control a variety of mice EBV-related cancers in the model. More importantly, allogeneic Vδ2-T-Exos has a higher therapeutic effect in controlling EBV-related tumors. Own Vδ2-T-Exos Therefore, Vδ2-T-Exos prepared from healthy donors can be used to treat patients with EBV-related tumors, which is very beneficial for the clinical application of this new method. "

   These findings are very important for cancer immunotherapy. First of all, Vδ2-T-Exos has strong immunostimulatory properties, which means it is designed as a cancer vaccine. This shows that it can act as an immune adjuvant and deliver immunogens. Second, Vδ2-T-Exos is superior to other exosome therapies (such as NK-Exos and DC-Exos), with dual anti-tumor activity and easy preparation; third, allogeneic Vδ2-T-Exos has higher anti-tumor properties effect. Compared with the preparation of autologous Vδ2-T-Exos and allogeneic exosomes, the clinical feasibility of Vδ2-T-Exos can be significantly improved because it does not require a separate procedure. From the perspective of quality control, standardization and centralization, it can be used clinically.