EE-ASI

Beta cell preservation via antigen-specific immunotherapy in Type 1 Diabetes: Enhanced Epidermal Antigen Delivery Systems

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 Obiettivo del progetto (Objective)

'Current approaches to improving glycaemic control in type 1 diabetes are centered on increasingly complex insulin delivery systems. However, less than 30% of patients can achieve target levels of glucose control with this approach even in a clinical trial setting and many patients are either unable or unwilling to make the personal commitment required. By contrast, preservation of even small amounts of endogenous insulin production, has been shown to improve glycaemic control, reduce hypoglycaemia, improve quality of life and reduce long-term complications. Importantly, glycemic control in the presence of endogenous beta cell function is not demanding and hence would be effective across the full spectrum of individuals. Antigen specific immunotherapy (ASI) is the preferred approach to beta cell preservation since this avoids the risks of immunosuppression. Attempts at ASI to date although successful in preclinical models have had limited efficacy in humans. There is therefore an urgent need for the development of novel approaches to deliver effective ASI. Our Enhanced Epidermal – Antigen Specific Immunotherapy (EE-ASI) system represents an innovative approach to ASI created by combining technologies brought by our academic and 2 SME partners. A beta cell target T cell epitope (proinsulin C19-A3) will be combined with the tolerogenic cytokine IL-10 and targeted to antigen presenting cells via gold nanoparticles and delivery into the very superficial layers of the skin using microneedles. Validation of manufacture, in vitro and in vivo preclinical efficacy will be demonstrated followed by a phase 1 clinical trial to confirm safety in humans. We anticipate that the EE-ASI system will be less costly, more effective and more acceptable to patients in improving glycaemic control than exogenous insulin replacement. Intellectual property, regulatory and ethical issues will be carefully addressed in order to maximise exploitation of this integrated system for the benefit of the SMEs.'

Introduzione (Teaser)

European researchers are pursuing an innovative vaccination approach to halt the immune-mediated nature of type I diabetes. The disease-modifying breakthrough could improve the life of millions of diabetes sufferers.

Descrizione progetto (Article)

Type I diabetes is an autoimmune disorder where the immune system attacks and destroys the pancreatic beta cells responsible for insulin production. This is a gradual process and most patients have residual insulin levels at the time of diagnosis.

Individuals with residual insulin exhibit better glycaemic control and fewer long-term complications than those with no insulin. Considerable effort has been directed towards halting the immune attack against beta cells and preserving even low level insulin production.

Research is focusing on enhancing the activity of regulatory T cells. These cells recognise self-proteins and suppress any immune responses against them. Central to the success of this approach is the context in which the antigen is presented and the state of the antigen presenting cells (APCs).

The aim of the EU-funded http://www.ee-asi.eu/ (EE-ASI) (Beta cell preservation via antigen-specific immunotherapy in type 1 diabetes: enhanced epidermal antigen delivery systems) project is to investigate novel ways of delivering beta cell antigens to the immune system to produce tolerance rather than immunity.

The EE-ASI strategy combines a T cell targeting peptide with gold nanoparticle technology. This promotes a T cell tolerogenic phenotype and delivers bioactive cytokines at the same time. The idea is that this vaccine can be administered intra-dermally on a needs-basis to achieve the desired outcome.

Pre-clinical testing of the vaccine has validated that antigen presentation occurs through APCs and not due to protein diffusion to the draining lymph nodes. The next step in the project is to design and conduct a phase I clinical trial to test the safety of this novel immunotherapy approach for type I diabetes.

EE-ASI project outcomes will provide invaluable insight into the possibility of vaccinating to stop autoimmunity and preserve pancreatic beta cells function. If successful, this approach will revolutionise diabetes treatment and enhance the quality of life of many affected individuals.