A phase I toxicity trial of the herpes simplex virus HSV1716 in patients with oral squamous cell carcinoma, with an in vitro investigation of the cytotoxic effects of HSV1716 alone and in combination with cisplatin in head and neck sqaumous cell carcinoma

Mace, Alastair T.M (2007) A phase I toxicity trial of the herpes simplex virus HSV1716 in patients with oral squamous cell carcinoma, with an in vitro investigation of the cytotoxic effects of HSV1716 alone and in combination with cisplatin in head and neck sqaumous cell carcinoma. MD thesis, University of Glasgow.

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Abstract

Head and neck squamous cell carcinoma (HNSCC) is a challenging disease which causes significant morbidity and mortality. Tobacco and alcohol are the prime aetiological factors and incidence rates are much higher among people from deprived areas. Too many patients present with advanced disease. Unfortunately the substantial advances in established therapies, including surgery, radiotherapy and chemotherapy, have not had a significant impact on patient survival. Treatment failure is a significant problem and there is a great need for the development of novel therapies. Oncolytic viruses have been developed to selectively infect, replicate in and kill targeted cancer cells, while leaving healthy normal cells alone. HSV1716 is an avirulent HSV-1 mutant with a 759 bp deletion in both copies of the RLl gene (MacLean et al, 1991). HSV1716 has been characterised as a selectively replication competent virus and a potential novel cancer therapy. HSV1716 has not been previously investigated in HNSCC. The aims of this thesis were to determine whether HSV1716 would replicate in and kill head and neck squamous cell lines, to determine if the cytotoxic effects in vitro were enhanced when combined with the conventional chemotherapeutic agent cisplatin and to carry out a phase I clinical safety trial involving the preoperative intratumoural injection of HSV1716 in patients with oral squamous cell carcinoma. The principal problem areas involve optimising the delivery and distribution of HSV1716 into a dense heterogeneous SCC tumour cell matrix. Increasing our knowledge of the interactions between HSV1716, the fINSCC tumour cell and the immune system will help to optimise antitumour efficacy. This will maximise its ability to disseminate throughout a tumour mass and endure efficacy, despite encountering the immune response. Current therapies for recurrent head and neck cancer, such as tumour debulking, further irradiation and chemotherapy have all produced poor responses of limited duration, and significant morbidity. HSV1716 has the potential to complement and improve conventional therapies. (Abstract shortened by ProQuest.).

Item Type: Thesis (MD)
Qualification Level: Doctoral
Additional Information: Advisers: Moira Brown; David Soutar
Keywords: Pharmacology, Virology
Date of Award: 2007
Depositing User: Enlighten Team
Unique ID: glathesis:2007-71012
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 09 May 2019 14:28
Last Modified: 09 May 2019 14:28
URI: http://theses.gla.ac.uk/id/eprint/71012

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