A genetically engineered virus, delivered intravenously, is being readied for a first-in-human trial against pancreatic cancer. Pancreatic ductal adenocarcinoma (PDAC) kills nearly all who get it. In the UK, 10,000 new cases appear each year, and incidence is expected to rise 6% by 2035. Existing immunotherapies that work for other cancers fail here because PDAC actively shuts down the body’s immune response. This project tackles that failure head-on. The virus, called VVL-21, is an oncolytic vaccinia virus designed to selectively replicate inside tumour tissue. It kills cancer cells directly and, crucially, inflames the tumour’s microenvironment—recruiting immune cells into a site that normally excludes them. In preclinical work, VVL-21 boosted the effectiveness of an approved anti-PD1 immunotherapy, creating a powerful combination. Because it can be injected into a vein, it can reach metastatic deposits that current oncolytic viruses, which must be injected directly into a tumour, cannot. If the team succeeds in generating the required manufacturing and toxicity data, they will seek MHRA approval for a Phase I clinical trial. Success would open a new treatment avenue for a cancer that has seen almost no therapeutic progress in decades.
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Pancreatic Ductal Adenocarcinoma (PDAC) is an almost uniformly lethal disease. In the UK alone, 10,000 cases are reported each year and the incidence rates are expected to rise by a further 6% by 2035. While a number of cancers are responding favourably to new immunotherapeutic treatment protocols, including vaccination and checkpoint blockade, these strategies have failed to impact PDAC survival rates, because PDAC is potently able to prevent the host immune system controlling cancer progression. Thus, there is an urgent need to design new types of therapy to overcome the barriers to conventional therapy in PDAC. We have developed novel tumour-targeting oncolytic viruses (TOVs), which are attractive therapeutic options for cancer. These agents can, through selective replication in the tumour tissue, amplify the input dose and kill tumours by multiple mechanisms, including direct cell killing and importantly by induction of systemic anti-tumour immune responses in the patient that can target primary tumour, metastatic deposits and prevent recurrence. In addition, TOVs can act as delivery vectors, delivering immune stimulants to amplify the immune response against tumour-specific antigens that are expressed only by tumour cells, allowing the immune system to specifically recognise and kill tumour cells. We have recently developed a new generation of TOVs called VVL-21. This new biological therapeutic agent can inflame the tumour micro-environment, promoting infiltration of multiple immune cells within pancreatic tumours. Strikingly this new agent can boost the efficacy of an approved immunotherapy agent anti-PD1 and together these agents provide a powerful therapeutic platform for treatment of pancreatic cancer. Additionally, our new therapeutic agent can be injected intravenously,which will allow targeting of metastatic cancers. These are currently targeted inefficiently by TOVs as most clinically advanced TOVs must be delivered intra-tumourally to achieve therapeutic benefit. In this project, we aim to to achieve sufficient experimental data, including large scale manufacture of the virus to GMP standard and toxicity testing in order to get an approval by the MHRA for a Phase I clinical trial of this novel virus to treat pancreatic cancer, providing hope for improved prognosis for pancreatic cancer patients.
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