Novel therapeutic approach against Epstein-Barr virus-associated tumors


Date:
October 11, 2020
Source:
The University of Hong Kong
Summary:
A research team hsd discovered that certain exosomes can effectively
control Epstein-Barr virus-associated tumors and induce T-cell
anti-tumor immunity. The novel findings provide insights into new
therapeutic approach for Epstein-Barr virus (EBV)-associated tumors.



FULL STORY ==========================================================================
A research team at LKS Faculty of Medicine, The University of Hong Kong (HKUMed) discovered that exosomes derived from V?2-T cells (Vd2-T-Exos)
can effectively control Epstein-Barr virus-associated tumours and
induce T-cell anti-tumour immunity. The novel findings of Vd2-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 (Vd2-T-Exos) remains unknown.

Research findings Herein, the team found that Vd2-T-Exos contained death-inducing ligands (FasL and TRAIL) and immunostimulatory molecules
(CD80, CD86, MHC class I and II).

Vd2-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 Vd2-T-Exos effectively
controlled EBV-associated tumours in immunodeficient and humanized
mice. Because expanding V?2-T cells and preparing autologous Vd2-T-Exos
from cancer patients ex vivo in large scale is challenging, the team
further explored the anti-tumour activity of allogeneic Vd2-T-Exos
in humanized mouse cancer models. Interestingly, the team found that
allogeneic Vd2-T-Exos had more effective anti-tumour activity than
autologous Vd2-T-Exos in humanized mice; the allogeneic Vd2-T-Exos
increased the infiltration of T cells into tumour tissues and induced
more robust CD4 and CD8 T cells-mediated anti-tumour immunity. Compared
with exosomes derived from NK cells with direct cytotoxic anti-tumour
activity or dendritic cells that induced T-cell anti-tumour responses, Vd2-T-Exos have dual anti-tumour activities by directly killing tumour
cells and indirectly inducing T cells- mediated anti-tumour responses,
thus resulting in more effective control of EBV-associated tumours.

"Our study provides the first evidence about the anti-tumour activities
of Vd2- T-Exos against EBV-associated tumours. These exosomes could
effectively control EBV-associated cancers in multiple mouse models. More importantly, allogeneic Vd2-T-Exos had higher therapeutic efficacy than autologous Vd2-T-Exos to control EBV-associated tumours. Therefore, the Vd2-T-Exos prepared from healthy donors can be used to treat patients
with EBV-associated tumours, which is highly beneficial to the clinical application of this novel approach," said Professor Tu Wen-wei, Antony and
Nina Chan professor in Paediatric Immunology, Department of Paediatrics
and Adolescent Medicine, HKUMed, who led the research.

Significance of the study The findings of the study have significant implications in cancer immunotherapy. Firstly, the identification that Vd2-T-Exos has potent immunostimulatory property suggests that they
could be designed as a cancer vaccine by serving as immune adjuvant
and delivering immunogens. Secondly, the Vd2-T-Exos has advantages over
other exosome-based therapies (e.g. NK-Exos and DC-Exos) by displaying
dual anti-tumour activities and are easier in preparation. Thirdly, the
results that allogeneic Vd2-T-Exos have higher anti- tumour efficacies
than autologous Vd2-T-Exos can greatly enhance the clinical feasibility
of Vd2-T-Exos, because the preparation of allogeneic exosomes does
not require personalized procedures and is easier in quality control, standardization and centralization for clinical application.


========================================================================== Story Source: Materials provided by The_University_of_Hong_Kong. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Xiwei Wang, Zheng Xiang, Yinping Liu, Chunyu Huang, Yujun Pei,
Xia Wang,
Hui Zhi, Wilfred Hing-Sang Wong, Haiming Wei, Irene Oi-Lin
Ng, Pamela Pui-Wah Lee, Godfrey Chi-Fung Chan, Yu-Lung
Lau, Wenwei Tu. Exosomes derived from Vd2-T cells control
Epstein-Barr virus-associated tumors and induce T cell antitumor
immunity. Science Translational Medicine, 2020; 12 (563): eaaz3426
DOI: 10.1126/scitranslmed.aaz3426 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/10/201011220803.htm

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