Rebalancing the immune system to treat 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 â€“ most
therapeutics focus on relieving inflammation and the pain associated with it.
Drug Target Reviewâ€™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 â€˜bad guysâ€™ of course, but
there are also â€˜good guysâ€™ in the immune system, which help to fight or control
autoimmune attacks,â€ 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
Dr Poirierâ€™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.
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, â€œthey turned out to be traumatically toxic in humans,
because they activate the receptors and as a result the whole immune system.â€
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 â€œeach time we have an expansion of memory T cells which recognise
autoantigens, we have a relapse of the disease.â€
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.
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.
also highlighted that progression in R&D models, such as ex vivo patient
tissue samples, should also contribute to future success and drug discovery