Having survived millions of years of evolution amongst primates, Epstein Barr virus (EBV) is considered one of the most complicated viruses. It not only causes primary infectious mononucleosis but also has the ability to transform itself into an oncogenic virus. Recent evidence strongly correlates EBV to various autoimmune diseases such as multiple sclerosis.
These diseases are usually treated with traditional approaches including ectomy and radio/chemotherapy, with the addition of monoclonal antibodies in some cases. Limited therapeutic progress has led to increased interest in the capacity for immunotherapy in the targeted treatment of EBV associated diseases. Strong evidence supporting the role of dysfunctional T cells in EBV cancers, has already led to the development of immunotherapies for EBV lymphomas. However, this approach warrants further studies with regard to testing the efficacy, safety and prolonged survival of infused immune cells for the targeted attack of virus/ virus transformed cells in vivo.
Importantly, these studies require an animal model that replicates the disease in a manner that is homologous to the human setting. Owing to the limited tropism of the virus, the generation and optimization of humanized murine models is still needed. The Translational and Human Immunology lab, at QIMRB, has developed a humanized murine model that enables us to replicate latent EBV cancer in vivo.
Using this model, my project aims to profile the immune landscape and evaluate immunotherapies in vivo. This model enables the prophylactic or therapeutic transfer of adoptive T-cell immunotherapies. Contrary to mature PBMC injection in SCID mice, these do not cause graft- versus- host disease and are EBV negative universally.
Additionally, this model provides us with a platform to investigate the underlying immunological, virological and serological parameters of EBV associated lymphomas and other EBV-associated autoimmune conditions. It provides a powerful resource for the characterization of viral trafficking, and histopathology analysis enabling us to demonstrate spatial configuration of immune cells in relation to EBV virus. Importantly, this model enables us to examine the temporal activity of cytotoxic lymphocytes as a therapy for EBV-associated tumours.