Qu Biologics has developed a platform of immunotherapies called Site Specific Immunomodulators (SSIs). SSIs are derived from components of inactivated bacteria, designed to restore the body’s normal immune function to treat immune-related diseases such as inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC). In IBD, unlike current treatments that suppress the immune system, SSIs are designed to restore the body’s innate immune system and correct the dysfunctional immune response.
Dr. Hal Gunn explains how Qu Biologics’ QBECO SSI may work to restore innate immune function
Restoring our body’s normal healthy immune function
For millions of years, acute infection was the major selective force for the evolution of the immune system. Our immune system is remarkably adept at responding to acute infection, and our body’s response to acute infection helps us preserve and maintain optimal immune function. A lack of immune system stimulation by acute infection can lead to chronic immune system dysregulation, resulting in an increased risk of cancer and other chronic inflammatory diseases. This concept is commonly referred to as the ‘hygiene hypothesis’ –that we may be living in ‘too clean’ a world and our immune system is not getting sufficient stimulation to maintain optimal health.
Qu Biologics has discovered the underlying mechanism of the ‘hygiene hypothesis’ – the mechanism by which our immune system’s response to acute infection helps us fight chronic inflammatory diseases. Qu Biologics’ Site Specific Immunomodulators (SSIs), derived from bacterial components, are designed to harness this natural response, restoring normal immune function and our body’s innate capacity to heal.
Chronic inflammatory disorders, such as Crohn’s disease and ulcerative colitis, stem from and perpetuate chronic immune dysfunction that, if left unchecked, can lead to progressively deteriorating health. Many current treatments for IBD suppress or disable the immune system rather than restore normal immune function. At Qu Biologics, we recognize that sustainable recovery from diseases is contingent upon restoring healthy immune function and harnessing our body’s natural ability to heal. It is with this central aim that Qu Biologics has developed SSIs that are designed to activate the body’s innate immune system to re-establish balance and normal healthy immune function.
SSIs are designed to restore the body’s normal immune response
In order to understand how SSIs work, it is helpful to know about the two complementary parts of our immune system. Our immune system consists of two main components, referred to as the innate and adaptive immune systems. The adaptive immune system is highly specific – a specific antibody or specific memory T-cell produced to attack a specific antigen – and relies on past exposure to tailor a very specific immune response to a very specific threat. The innate immune system, on the other hand, responds immediately to danger and is very non-specific – when stimulated, cells of the innate immune system clear up whatever is not supposed to be there, including bacteria, cancer cells and dead and dying cells. This makes the innate immune system pivotal as the first line of defence and for guiding a normal healthy immune response against a wide variety of threats.
Cancer is associated with a ‘suppression’ of the adaptive immune system in the tumour – an inability of the adaptive immune system to recognize and clear cancer cells. On the other hand, the symptoms of IBD (Crohn’s disease, ulcerative colitis) and autoimmune disease are due to an ‘overreaction’ of the adaptive immune system, resulting in damage and inflammation. While cancer and inflammatory bowel disease are opposite diseases from the perspective of the adaptive immune system, they share the same underlying pathology – a defect/deficiency/suppression of the innate immune system, specifically, a very important cell of our innate immune system, macrophages, which means ‘big eater’.
Historically, treatments for inflammatory bowel disease have been focused on suppressing the adaptive immune system. Since the normal functioning of our immune system is important for our body’s health and normal response against infection and cancer, these treatments can be associated with significant side effects, including an increased risk of serious infection and some cancers. Qu Biologics is approaching the treatment of these diseases (CD and UC) in an entirely different way – by restoring the innate immune system and our body’s normal immune response and capacity to heal.
Chronic inflammatory disorders are linked to defective macrophage function
Macrophages, important sentinel cells of the innate immune system, are derived from a type of white blood cell called monocytes, which circulate through the body in search of ‘trouble’. When they receive a danger signal from a specific organ or tissue, monocytes move into that tissue where they undergo a series of changes to become tissue-associated resident macrophages, which allow them to ingest (or “phagocytose”) invading pathogens or cancer cells and remove dead or damaged cells that cause inflammation. Resident macrophages stay on guard for months monitoring the environment to make sure that the proper barriers are working and that there is nothing out of line disturbing normal tissue function. By playing these important roles, macrophages are essential in ensuring tissue health and normal immune function. There is growing evidence that disruption of proper macrophage function may underlie cancer and other immune related diseases, such as Crohn’s disease and ulcerative colitis.
The role of macrophages in inflammatory bowel disease
There is a growing recognition and body of evidence that macrophage defect / deficiency / immunosuppression plays an important underlying role in IBD, including Crohn’s disease and ulcerative colitis. There are several hundred gene abnormalities associated with IBD that increase the risk for these diseases, many of which are associated with reduced macrophage function1 and, specifically, reduced ability of macrophages to optimally clear bacterial infection2. While most people with these gene abnormalities never develop Crohn’s disease or ulcerative colitis, it is thought that an environmental trigger in genetically susceptible individuals with reduced macrophage function may set up a chronic inflammatory stimulus that results in sustained immune dysfunction, including an over-reactive adaptive immune response that causes further ongoing inflammation and damage.
People with active Crohn’s disease have monocytes / macrophages that are unproductively immunosuppressive.3-5 These immunosuppressive macrophages have a reduced ability to clear bacterial infection in the gastrointestinal tract, which may lead to dysbiosis (i.e., reduction in healthy commensal bacteria in the GI tract and an overgrowth of pathogenic bacterial species) and invasion of the mucosal lining of the GI tract with multiple pathogenic species. Without the support of immunocompetent macrophages, it is hypothesized that these immunosuppressed macrophages (depicted in orange in illustration below) are unable to clear the bacterial infection (depicted in blue in illustration below), resulting in chronic inflammation and tissue damage. The adaptive immune system reacts against the chronic infection, resulting in further inflammation, tissue damage and symptoms, but without the support of immunocompetent macrophages, this over-reactive adaptive immune response is unable to clear the chronic infection/dysbiosis.
Current treatments for Crohn’s disease and ulcerative colitis (e.g., prednisone, Imuran®, Remicade®, Humira®, etc.) suppress this over-reactive adaptive immune response. In the portion of patients in whom these treatments are effective, these treatments reduce the inflammation and symptoms of the disease, but these treatments do not treat what may be the underlying cause of the disease (i.e., innate immune system dysfunction, dysbiosis, and chronic bacterial infection), so not surprisingly, when these treatments are discontinued, symptoms typically recur. Suppressing the adaptive immune system is also associated with significant potential side effects.
Restoring immunocompetent macrophage function may be central for resetting productive immune responses
SSI treatment for Crohn’s disease and ulcerative colitis is designed to recruit activated immunocompetent macrophages (depicted in green in illustration below) to the gastrointestinal tract, resulting in the clearance of dysbiosis and the resolution of chronic bacterial infection. Once this underlying trigger is removed, there is no longer any pathology for the adaptive immune system to respond against, resolving the chronic inflammation and restoring normal immune function and health. In other words, Qu’s SSIs are specifically designed to reboot normal macrophage function in the diseased organ, re-instating the normal innate immune response required to restore health.
By restoring normal functioning of the innate immune system, SSIs are designed to restore and effectively mobilize the natural healing abilities of the body – an approach that we believe best serves long-term sustainable health.
- Mokry, M. et al. Many inflammatory bowel disease risk loci include regions that regulate gene expression in immune cells and the intestinal epithelium. Gastroenterology146, 1040–7 (2014).
- Vavricka, S. R. & Rogler, G. New insights into the pathogenesis of Crohn’s disease: are they relevant for therapeutic options? Swiss Med. Wkly.139, 527–34 (2009).
- Hayee, B., Rahman, F. Z., Sewell, G., Smith, A. M. & Segal, A. W. Crohn’s disease as an immunodeficiency. Expert Rev. Clin. Immunol.6, 585–96 (2010).
- Marks, D. J. B. et al. Defective acute inflammation in Crohn’s disease: a clinical investigation. Lancet367, 668–78 (2006).
- Marks, D. J. B., Rahman, F. Z., Sewell, G. W. & Segal, A. W. Crohn’s disease: an immune deficiency state. Clin. Rev. Allergy Immunol.38, 20–31 (2010).
Other Scientific Literature
- Karaiskos C, Hudspith B N, Elliott T, et al. Defective macrophage function in crohn’s disease: role of alternatively activated macrophages in inflammation. Gut 2011; 60:A143-A144 Gersemann M, Wehkamp J, Stange EF. Innate immune dysfunction in inflammatory bowel disease. Journal of internal medicine 2012;271(5):421-8.
- Korzenik JR. Is Crohn’s disease due to defective immunity? Gut 2007;56(1):2-5.
- Marks DJ. Defective innate immunity in inflammatory bowel disease: a Crohn’s disease exclusivity? Current opinion in gastroenterology 2011;27(4):328-34.
- Marks DJ, Harbord MW, MacAllister R, et al. Defective acute inflammation in Crohn’s disease: a clinical investigation. Lancet 2006;367(9511):668-78.
- Marks DJ, Rahman FZ, Sewell GW, Segal AW. Crohn’s disease: an immune deficiency state. Clinical reviews in allergy & immunology 2010;38(1):20-31.