More than 90% of people carry Epstein-Barr virus, and it causes around 200,000 new cancers each year—yet there is no vaccine or drug to stop it. This matters because the virus, first discovered in a Burkitt lymphoma tumour decades ago, is a proven human oncogenic virus. It drives a range of malignancies, but exactly how it evades the immune system in otherwise healthy people remains poorly understood. The researchers aim to identify the specific immunological failures that allow the virus to trigger cancer. If successful, this work could lead directly to new treatments. The team will develop tools to profile T-cell immunity against EBV, then use those tools to monitor a poxvirus-based vaccine designed to generate T-cell responses that target virus-infected cells. They will also create bispecific T-cell receptor reagents that redirect the immune system to attack established EBV-associated tumours. These are not distant possibilities—the project explicitly aims to produce immunotherapies with immediate translational potential for human health, addressing a global cancer burden that currently has no targeted medical options.
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Epstein-Barr virus (EBV) infects >90% of the human population and is associated with a broad spectrum of diseases, including an array of distinct malignancies. Indeed, EBV was first isolated from a Burkitt lymphoma tumour specimen almost 50 years ago and represents the prototype human oncogenic virus. The global burden of EBV-associated malignancies is startling, with approximately 200,000 new cases reported annually. At present, however, there are no commercially available vaccines, no effectiv e antiviral drugs and no virus-targeted therapeutics to prevent or treat these devastating malignancies. The research questions in this proposal reflect the pressing need for rational intervention in the EBV-associated oncogenic process, collectively aiming to identify pathways to prevention and cure. Novel immunotechnological approaches will be developed to profile EBV-specific T-cell immunity and reveal the immunological lesions that underlie the failure of immune surveillance in otherwise imm unocompetent individuals. These tools will also be used to monitor a poxvirus-vectored vaccine that aims to generate EBV-derived latent antigen-specific T-cell responses to correct the immune deficit and effectively target transformed B-cells. Further, novel bispecific high affinity T-cell receptor-based reagents will be developed to redirect T-cell immunity against established EBV-associated malignancies. Successful delivery and application of these cutting edge immunotechnologies and immunothe rapeutic strategies will have direct translational implications for human health.
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