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Title: A phase one clinical trial of dendritic cell immunotherapy in patients with advanced malignancy
Author: Nussey, Fiona Elizabeth
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2005
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The function of DC in patients with malignancy is deficient and re-administration of ex-vivo cultured DC may reverse this. MUC-1 is a trans-membrane glycoprotein which is aberrantly glycosylated in a number of human cancers such that an occult epitope is exposed which provides an immuno-therapeutic target. A phase 1 clinical trial of MUC-1 pulsed DC began in July 1999. 12 patients with breast, ovarian, colorectal and oesophageal cancer have been treated. Mononuclear cells were obtained from a peripheral blood donation or leucapheresis and adherent monocytes were cultured in GM-CSF and IL4 to obtain DC. These were then pulsed with a liposomal preparation of a 25-mer peptide from MUC-1 (BLP-25, Biomira Inc) and re-administered by subcutaneous injection. DC were defined as cells expressing CD1a. Patients received between 0.075 x 106 and 1.0 x 106 DC per kg body weight in one or two doses. They were followed up for toxicity, immune response and clinical effects at days 1, 7, 14, 28 and 90. The maximum dose of DC administered in a single injection was 41 x 106 DC. There was little evidence of acute toxicity other than inflammation of the injection site. There was no good evidence of clinical benefit seen. Some evidence of increased cellular immune responses in general following DC therapy were seen which may be attenuated by an increase in the dose of DC administered, but few changes reached significance and there was little consistency. There was no consistent evidence of an increase in specific MUC-1 cellular responses following therapy.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available