Rebalancing the immune system to treat autoimmune disease

Admin on 13 / 03 / 2020 under Autoimmune Disease

Dr Nicolas Poirier reveals how immunotherapies can be designed to recalibrate the immune system for long-term maintenance of autoimmune remission.

Autoimmune conditions affect more than 23.5 million Americans and as many as one in four in the UK. According to recent statistics these conditions are on the rise and some, including Type I diabetes, are three times more common that a few decades ago. While treatments have been developed, there is no cure for autoimmune conditions – most therapeutics focus on relieving inflammation and the pain associated with it.

Drug Target Review’s Hannah Balfour spoke with Dr Nicolas Poirier, the Chief Scientific Officer (CSO) of OSE Immunotherapeutics, to understand their novel approach to targeting and treating autoimmune diseases; using immunology to rebalance the immune system.

A lot of companies focus on inhibiting or killing immune cells, but what we have learned in the last five to 10 years is that not all immune cells are pathogenic. There are ‘bad guys’ of course, but there are also ‘good guys’ in the immune system, which help to fight or control autoimmune attacks,” explained Dr Poirier. He clarified that for each immune cell, there is a corresponding regulatory subtype, such as the well-known T regulatory (Treg) cells. B cells also have a regulatory subtype and so do macrophages.

Dr Poirier’s team target their products to specifically inhibit the pathogenic cells and activate the regulatory cells, manipulating the balance of the immune system to reduce autoimmunity. While this may have various short-term effects on disease symptoms, the overarching goal is to maintain remission and prevent flare-ups in the long term.

Current OSE immunotherapies

At present, the company has two therapeutics in trials, which, according to their CSO, have similar effects but utilise different biologic mechanisms of action.

Both are therapies using monoclonal antibody (mAb) fragments as their active pharmaceutical ingredient (API). Dr Poirier revealed the use of fragments was particularly important in establishing a safe level of toxicity.

OSE-104 is a mAb fragment therapy which selectively binds to the CD28 T-cell receptor to block activation of T cells that have the potential to be pathogenic. They also discovered that their fragment can promote Treg cell expansion.According to Dr Poirier, other companies have attempted to develop similar therapies using full mAbs and despite working well in a murine model, “they turned out to be traumatically toxic in humans, because they activate the receptors and as a result the whole immune system.” Instead, his team developed antibody fragments large enough to specifically bind target receptors, but that are unable to activate the receptors they bind to, blocking them instead.

Memory T cells circulate for years after an initial infection and prompt faster future responses to their specific antigens. According to Dr Poirier, the production of memory T cells against autoantigens is responsible for the chronicity of autoimmune conditions such as IBD, because “each time we have an expansion of memory T cells which recognise autoantigens, we have a relapse of the disease.”

Dr Poirier also added that OSE-127 has a further action; IL-7 signalling effects transcription, promoting the proliferation and survival of T cells. By blocking this action, OSE-127 prevents the long-term survival of immune cells such as memory T cells.

Conclusion

Dr Poirier presents a novel approach for the treatment of autoimmune conditions, moving away from past techniques of broad immunosuppression and towards selectively activating and repressing different subtypes of immune cells. Moving forward, Dr Poirier suggests there will be further modification and development of their mAb fragments in order to target other immune cells related to different conditions.

He also highlighted that progression in R&D models, such as ex vivo patient tissue samples, should also contribute to future success and drug discovery