Peptide immunotherapy for Type 1 diabetes aims to restore tolerance to self, whilst leaving the rest of the immune system intact. Once the right peptide isdelivered to the right cell, it is important to closely monitor the effect of such atherapy, both in the regards to the immune and metabolic response. Clinical trials are designed to test the effect of a drug at the end of the trial period, which can be years later. Ex-vivo human models are not subject to extensive regulatory requirements, and can rapidly provide proof of principle on the efficacy of a treatment, which can be then translated to the clinic. I have shown that the skin organ bath culture is a useful system for studying treatment effects of variety of ex-vivo delivered agents. When used to optimise peptides delivery, it indicated a potential role of dry coated microneedles in targeting epidermal DCs, important because of their endogenous tolerogenic potential, which can be further modified by topical treatments and locally injected agents. Whether true tolerogenic potential can be achieved in such a way, is subject to further studies designed to optimise the type, dose and the duration of the treatment by the conditioning agent. My data also suggested that lymph node fine needle aspiration biopsy is a feasible non-invasive method suitable for monitoring the cellular immune responses after antigen skin delivery. Subject to confirmatory study, it has a potential to find immediate application as an efficient and reliable tool for monitoring immune response after antigen-specific immunotherapy in clinical trials. Once recognised as ‘immune responders’ in such a way, participants in clinical trials can be subjected to the monitoring of the metabolic response to the immune intervention, by measuring !-cell function via stimulated UCPCR as a non-invasive and more compliant-prone alternative to the standard MMTT.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:637150 |
| Date | January 2015 |
| Creators | Tatovic, Danijela |
| Publisher | Cardiff University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://orca.cf.ac.uk/69686/ |
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