Using the Innate Immune System to Treat Disease

For most people, two of the most frightening diseases are cancer and Alzheimer’s disease. The reason is simple – these diseases are incurable. The widespread fear of them goes much deeper. While many people are faced with the tragedy of seeing these illnesses take over the lives of family members, spouses, friends, and loved ones, there is a separate anxiety of experiencing one or both of these issues in one’s lifetime, as they both appear to “run in families.” In fact, with some exceptions, the occurrence of cancer and Alzheimer’s disease is sporadic which means that a clean family history does not mean you will be spared. In addition, the understanding of why these diseases occur and what we can do to either prevent or treat them is somewhat scant when compared to other debilitating conditions.

Historically, there has been little change in the way we approach the development of therapies for the treatment of cancer and neurodegenerative diseases. According to INmune Bio Inc., a clinical stage biotechnology company, this is part of the reason why a cure for these pernicious illnesses has eluded us. Rather than viewing cancer and Alzheimer’s as an oncologic and neurologic disease respectively, it would behoove us to start seeing them both as immunologic problems. Immunologic diseases are often driven by inflammatory cytokines. Targeting the immune system instead of cancer growth pathways or amyloid in Alzheimer’s disease is a completely different approach to therapy. The breakthrough concept being developed by Inmune Bio is that reprogramming the innate immune system, rather than the adaptive immune system, may be the path to treat both illnesses.

Adaptive and Innate Immune Systems: What’s the Difference?

The body’s immune system has two different parts: innate and adaptive.The innate immune system is used for general defense against a non-specific threat. It works extremely quickly, protecting the body like a knee-jerk reaction. The adaptive immune system, on the other hand, offers a specific response to a certain germ, antigen, or pathogen, usually because the body has encountered it before. The first confers a short-term response to danger. The latter confers life-long protection.

In most cases, immunotherapy for both cancer and Alzheimer’s disease has targeted the adaptive immune system, attempting to equip T cells with the tools it needs to fight these diseases. Inmune Bio’s approach is to reprogram the innate immune system to fight the problem. Naturally, this requires an entirely new way of viewing both disorders as well as the treatments available for them.

Why Focus on the Innate Immune System to Treat Cancer and Alzheimer’s?

A tumor is a mass of cells that divide without reason, becoming locally destructive and breaking off to form metastasis – sites of cancer far from the primary tumor. According to INmune Bio Inc., often more than half of the cells in the tumor are immune cells, the patient’s own immune cells that have been subverted to protect the cancer, not attack the cancer.  The company calls these protector cells – the majority of these protector cells are cells of the innate immune system, not adaptive immune cells. For this reason, INmune has developed therapies that target innate immune functions rather than adaptive functions, a novel approach in this field.

INB03, a biologic therapy is used to target and neutralize myeloid-derived suppressor cells (MDSC). MDSC are the Queen Bee of the TME (tumor microenvironment) because they recruit the many types of protector cells to the TME. Eliminating MDSC should make the patient’s immune system and immunotherapy more effective by decreasing the number and types of the protector cells in the TME. A second therapy, INKmune targets minimal residual disease (MRD). MRD is the cancer that comes back to cause relapse after the patient has been treated for their cancer. Many patients die of cancer relapse caused by MRD. Eliminating MRD is the job of natural killer cells (NK cells). INKmune is able to prime NK cells of the innate immune system to bind to tumor cells and kill them.3 The company is developing INKmune to eliminate MRD. Finally, INmune Bio is developing a therapy to target microglial cells of the brain. Microglial cells are macrophages of the brain that, when activated, cause nerve cell death and synaptic dysfunction, the hallmarks of Alzheimer’s disease. By eliminating microglial dysfunction, XPro1595, should cool neuroinflammation and prevent progressive cognitive decline. 

INB03 and XPro1595 work by targeting soluble TNF (Tumor Necrosis Factor). Neutralizing soluble TNF reverses the activation of MDSC and microglial cells. TNF biology is complicated; there are both toxic versions and helpful versions of TNF. Soluble TNF is the bad TNF and trans-membrane TNF is the good TNF. The ability to eliminate only soluble TNF is part of the reason why XPro1595 is so revolutionary. As Dr. C.J. Barnum, director of neuroscience and translational research at INmune Bio Inc., told SelectScience,2 “This is in contrast to the inhibitors currently available, which block all TNF activity – the good and the bad.” With thought leadership like this, it may be possible that serious and pioneering advances could be made in the next few years when it comes to treating both these rampant and as-yet-incurable diseases.

Immunologic Problems and Their Potential Solutions

The idea that both cancer and Alzheimer’s disease can be treated through targeting the innate immune system by eliminating single, toxic cytokine - soluble TNF,  is revolutionary. Currently, INmune Bio is at the forefront of this fight. After a single private financing round with no venture investors, the company is now a part of the public markets after a successful NASDAQ IPO in February of 2019.

The potential for “harnessing the power of the innate immune system”4 is groundbreaking and innovative, and could completely change the ways in which illnesses from cancer to neurodegenerative disorders and beyond are treated.

Sources and Citations
  1. https://www.ncbi.nlm.nih.gov/books/NBK279396/
  2. https://www.selectscience.net/editorial-articles/this-novel,-non-amyloid-approach-to-alzheimers-therapy-could-vastly-improve-outcomes/?artID=48655
  3. https://www.immunology.org/public-information/bitesized-immunology/cells/natural-killer-cells
  4. https://inmunebio.com/index.php/en/

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