T cell antibodies to treat diabetes
A new charity-biz collaboration is testing proteins that could prevent the immune system from destroying insulin secreting cells and help prevent the onset of diabetes.
MediGene has signed a two year deal with the Juvenile Diabetes Research Foundation (JDRF). The charity will pay €250,000 to help the Germany-headquartered biotech company advance its monoclonal T cell receptor (mTCR) therapeutics towards clinical trials. The soluble proteins are engineered to recognise intracellular antigens and block an immune system response by T cells.
These antigens are inaccessible for traditional monoclonal antibodies and so, the soluble T cell receptor technology opens a new field of options to target cancer, autoimmune, allergic and infectious diseases, according to the company.
Normally in Type I diabetics, receptors on the surface of T cells bind to antigens on pancreatic islet cells, which are responsible for the production of insulin. This marks them for destruction.
In its diabetes programme, MediGene has manufactured specific mTCRs which could bind to islet cell antigens, blocking them and preventing real T cell receptors from attacking the cells - “somewhat like taping over a keyhole to prevent a door from being unlocked,” according to the company.
MediGene also hopes the mTCRs could target known immunosuppressive agents to the islet cell’s local environment.
“Provided autoimmune destruction can be tamed, both the early diagnosis of pre-diabetic individuals and the recent advances in islet transplantation therapy offer the prospect of patients being able to maintain endogenous insulin production, with consequent improvements in quality of life,” said Dr Ulrich Delvos, chief operating officer at MediGene.
“MediGene’s mTCR technology holds the promise of tackling the underlying cause of this autoimmune disease.”
Dr Neill MacKenzie, MediGene’s head of commercial strategy and business development, explained to DrugResearcher.com that strategies to replace the body’s insulin directly or improve its ability to produce and use insulin do not prevent many side effects such as blindness, heart attacks, loss of limbs and kidney function.
MediGene hope to overcome this by creating a “therapy that tries to maintain some level of islet functioning,” said Dr MacKenzie. He explained that the mTCRs are currently in preclinical testing and it would be “at least a couple of years before first-in-man trials.” That is partly because animal models of diabetes take time to generate and this slows research down: “First we have to generate diabetes, and then cure it,” said Dr MacKenzie.
Dr MacKenzie explained that the technology’s main other application is in cancer where it could be used in exactly the opposite way - to activate an immune response and kill tumour cells. He also said that early on, MediGene had looked at using mTCRs as a drug delivery mechanism but it is not looking into it anymore because it “doesn’t think it has enough power”.
If, in the future, they decided to resurrect this research, Dr MacKenzie pointed to Wyeth’s Mylotarg (gemtuzumab ozogamicin) product as an example of how it might be achieved. Mylotarg is an anticancer drug composed of an antibody attached to a toxic antitumor antibiotic.
JDRF also supports other industry diabetes research, including studies at AGTC, Develogen, ESI, Genzyme, Novocell, Macrogenics and Tolerx. The last two are the most advanced research sponsored by the charity with both companies conducting Phase II trials of antibodies that target the CD3 T cell receptor called CD3. Both therapies aim to disarm T cells once they have become activated to attack islet cells.
“Targeted delivery of therapeutics is an attractive prospect,” said Dr Richard Insel, head of research at JDRF.
“This collaboration between MediGene and JDRF provides an exciting opportunity to validate the concept, and hopefully identify a lead compound for entry into the clinic.”
Talking about the JDRF support, Dr MacKenzie said: “It could hopefully lead to a much bigger grant - if we’re successful.”
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