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Title: Immunotherapeutic approaches in the treatment of melanoma
Author: Donnelly, Oliver
ISNI:       0000 0004 2744 4007
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2012
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Immunotherapeutic approaches to treat cancers have been pursued for many years with very little success. However recent success in the treatment of melanoma, have confirmed the potential utility of the approach. Oncolytic viruses are emerging therapies that work in part by directly killing cells they infect, but also by stimulating anti tumour immune responses. Radiotherapy is generally considered an immune suppressive treatment but recent preclinical evidence suggests that it can render cancer cells susceptible to immune mediated attack and generate anti tumour immunity when combined with additional therapies. In the work described measles virus, a potential oncolytic virus, kills human melanoma cells, both immortalised cell lines and freshly resected primary cells, and generates an inflammatory pattern of cytokines, chemokines and danger signals as it does so. The virus, and virus treated cancer cells enhance innate effector cells and mature dendritic cells. Virally treated melanoma cells stimulate adaptive T-cell anti melanoma responses. External beam radiotherapy in the palliative dose range was combined with combinations of adoptive cell therapy and vesicular stomatitis virus and did not enhance therapy. Sealed source brachytherapy was also combined with adoptive cell therapy and virotherapy but without synergy. In order to study the effects of existing and proposed immunotherapeutic approaches against melanoma that has metastasised to the brain, a model of intracranial melanoma was established and in initial therapy experiments survival was improved following treatment with intravenous oncolytic virotherapy. Immunotherapeutic approaches hold promise for the treatment of melanoma. Clinical testing of measles virus in trials with patients suffering from metastatic melanoma should be considered.
Supervisor: Melcher, A. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available