• Immunotherapy for Autoimmune Diseases

    Immune cells interacting in an autoimmune response, highlighting innovative immunotherapy solutions for autoimmune diseases.

    Posted on Jun 7, 2024

    Blog Highlights:

    • What causes autoimmunity?
    • Antibodies and BiSpecific antibodies for autoimmunity
    • Cellular treatments for autoimmunity
    • How can Marin Biologic Laboratories help you

    What Are Common Autoimmune Diseases?

    1. Type 1 Diabetes (T1D)

    The immune system destroys insulin-producing cells in your pancreas, resulting in high blood sugar. This damages the blood vessels and organs such as heart, kidneys, eyes and nerves.  The cause of type 1 diabetes is unknown, there is a genetic disposition   It usually strikes patients early in childhood. The prevalence is 38 million individuals, 12% of the US population.

    2. Rheumatoid arthritis (RA)

    Your immune system produces antibodies attack the joints, causing inflammation, swelling, and pain. If left untreated, RA gradually causes permanent joint damageTreatments include various medications that reduce immune system overactivity. About 1.3 million adults are afflicted with RA.

    3. Psoriasis/psoriatic arthritis

    Skin cells grow and then shed when they’re no longer needed. Psoriasis causes skin cells to multiply too quickly. The extra cells build up and form inflamed patches. On lighter skin tones, patches may appear red with silver-white scales of plaque. On darker skin tones, psoriasis may appear purplish or dark brown with gray scales.  Up to 30% of the 1.2 million people in the US with psoriasis also develop psoriatic arthritis. This can cause joint symptoms that include swelling, stiffness, and pain.

    4. Multiple sclerosis

    Multiple sclerosis (MS) damages the protective coating surrounding nerve cells (myelin sheath) in your central nervous system. Damage to the myelin sheath slows the transmission speed of messages between your brain and spinal cord to and from the rest of your body. This damage can lead to numbness, weakness, balance issues, and trouble walking. MS affects about 1 million people in the US.

    5. Systemic lupus erythematosus (SLE)

    Although doctors in the 1800s first described lupus as a skin disease because of the rash it commonly produces, the systemic form, which is most common, actually affects many organs. This can include joints, kidneys, brain, and heart.Common symptoms included joint pain, fatigue and rashes.  SLE affects about 0.3 million in the US.

    Other examples are Graves’ disease, Sjögren’s disease, scleroderma, and Hashimoto’s thyroiditis.

    Other pathological immune diseases. In autoimmunity, the immune system attacks self components that are pathologically seen as foreign. Often linked with these diseases are conditions where the immune system overreacts in response to other stimuli. These conditions include Ulcerative Colitis (UC), Crohn’s Disease (CD), Inflammatory bowel disease (IBD), Addison’s disease, and celiac disease.

    What causes autoimmunity?

    Autoimmunity occurs when the immune system mistakenly targets and attacks the body’s own cells and tissues.  Some of the causes are:

    • Genetic predisposition: There is often a genetic component to autoimmune diseases. Certain genes may increase the likelihood of developing an autoimmune condition. However, having these genes doesn’t guarantee that someone will develop autoimmunity.
    • Environmental triggers: Various environmental factors, such as infections, exposure to certain substances, and other external stimuli, can trigger an autoimmune response in individuals with a genetic predisposition. For example, infections may stimulate the immune system in a way that leads to the recognition of self-tissues as foreign. Infections with Epstein Barr Virus (EBV, “kissing disease”) and certain bacteria are linked to several autoimmune diseases.
    • Hormonal factors: Autoimmune diseases are more common in women than in men, suggesting a hormonal influence. Changes in hormone levels, especially during puberty, pregnancy, and menopause, may affect the immune system and contribute to the development of autoimmunity.
    • Dysregulation of immune system checkpoints: The immune system has mechanisms in place to distinguish between self and non-self antigens. T cells and B cells, which are crucial components of the immune system, undergo a process called central tolerance to avoid attacking the body’s own tissues. When this process is disrupted or if there are defects in the regulation of immune checkpoints, the immune system may mistakenly target self-antigens.
    • Stress: Chronic stress can have a negative impact on the immune system, potentially contributing to the development or exacerbation of autoimmune disorders. Stress hormones may influence immune function and increase the risk of autoimmune reactions.

    Professional doctor in a modern medical facility, representing expertise in immunotherapy for autoimmune diseases.

    Antibody Treatments for Autoimmunity

    The first therapeutic antibody, mouse OKT3, was used to suppress graft rejection by killing CD3-bearing T lymphocytes.  It has been supplanted by human or humanized antibodies against various aspects of T lymphocytes that kill foreign cells of grafts (graft rejection) and kill the insulin producing cells of the pancreas type I Diabetes (T1D).

    Antibodies to TNF, IL-4, IL-6, IL-13, IL-17, and IL-23 have revolutionized the treatment of autoimmune diseases, such as rheumatoid arthritis, ankylosing spondylitis, and psoriasis.

    • Dupixent is a monoclonal antibody that blocks the immune pathways that make up the type 2innate immune response (focused on extracellular defense and allergy generation), specifically those involving the cytokines interleukin-4 and interleukin-13 (IL-4 and IL-13, respectively). The drug was first approved in 2017 for use in treatment-refractory eczema. Approvals in asthmachronic rhinosinusitiswith nasal polyps, and the chronic disease eosinophilic esophagitis have since been added to the list.
    • Rituximab (Rituxan) is an anti-CD20 monoclonal antibody that kills B lymphocytes. It is approved for the treatment of non-Hodgkin lymphoma. Since some symptoms of autoimmune disease are mediated by antibodies produced by B lymphocytes, rituximab reduces the signs and symptoms of moderate to severe Rheumatoid Arthritis (RA). Multiple Sclerosis (MS) and Serum Lupus Erythematosus (SLE).
    • Anti–tumor necrosis factor (TNF) reagents

    Infliximab (Remicade) is an anti-TNF alpha monoclonal antibody that binds with high affinity to TNF-alpha and prevents the cytokine from binding to its receptors. It is approved for treating the symptoms of rheumatoid arthritis, and is used in combination with methotrexate. It is also approved for the treatment of symptoms of moderate-to-severe Crohn disease.

    Adalimumab (Humira) is another anti-TNF product. It is approved for use in reducing the signs and symptoms of moderate to severe rheumatoid arthritis, severe polyarticular juvenile rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and moderate to severe Crohn disease. It is also approved for the treatment of moderate to severe chronic plaque psoriasis.

    • Ulcerative Colitis (UC) and Crohn’s Disease (CD) are not autoimmune diseases but are examples of the body’s immune system reacting inappropriately to the bacteria that live in a person’s gut. Antibodies to TNF and to IL-23 are used for these diseases.

    Bispecific Antibody Treatments for Autoimmunity

    Bispecific antibodies are a type of therapeutic antibody designed to simultaneously target two different antigens.  Here are a few ways bispecific antibodies may be applied in the context of autoimmunity:

    Dual-targeting approach: Bispecific antibodies can be designed to simultaneously bind to both a disease-specific target and a regulatory molecule. By doing so, they aim to redirect the immune response, targeting harmful cells or molecules while also modulating regulatory pathways to prevent excessive immune activity.

    Immune cell redirection: Some bispecific antibodies are engineered to redirect immune cells to specific targets. For example, they might recruit regulatory T cells to dampen an inflammatory response or enhance the clearance of autoreactive cells.

    Cytokine modulation: Bispecific antibodies can be designed to neutralize or modulate the activity of cytokines involved in autoimmune processes. By simultaneously targeting a cytokine and a cell surface receptor, these antibodies disrupt the signaling pathways that contribute to inflammation and tissue damage.

    Autoimmune cell destruction: Bispecific antibodies can direct cytotoxic T cells to kill specific antibody producing or autoimmune inflammatory cells.

    Cellular Treatments for Autoimmunity 

    Cellular treatments for autoimmunity involve manipulating or modulating the activity of immune cells to restore immune balance and prevent the immune system from attacking the body’s own tissues. Here are a few cellular treatments for autoimmunity:

    • Hematopoietic Stem Cell Transplantation (HSCT): This involves the transplantation of hematopoietic stem cells, which can differentiate into various blood cells, including immune cells. HSCT aims to “reboot” the immune system by replacing the aberrant immune cells with new, non-autoreactive ones. It has been used in conditions like multiple sclerosis and systemic sclerosis.
    • T Regulatory (Treg) Cell Therapy: Regulatory T cells play a crucial role in maintaining immune tolerance and preventing autoimmunity. Researchers are investigating the possibility of using Treg cell therapy to boost the regulatory function of these cells. The goal is to enhance the immune system’s ability to suppress inappropriate immune responses.
    • Chimeric Antigen Receptor (CAR) T Cell Therapy: CAR T cell therapy, initially developed for cancer treatment, is being explored for autoimmune diseases. In this approach, T cells are genetically engineered to express a receptor that targets specific antigens involved in autoimmune processes. These modified T cells can then recognize and eliminate cells contributing to the autoimmune response.

    The rationale for using CAR-T in autoimmune diseases has to do with how the treatments work. For the autoimmune disease Lupus (systemic lupus erythematosus, SLE), a patient’s own immune cells are engineered to target a protein called CD19 that’s typically found on the surface of B cell cancers. But it appears these reactive cells can also destroy misfiring B cells that are responsible for the immune attack that inflammatory diseases like lupus inflict on the body.

    So far, the 15 patients in the study have been followed for a median of 15 months after their CAR-T infusions. All are doing well and have stopped taking immunosuppressive drugs. Two-thirds experienced a mild form of cytokine release syndrome, an immune side effect of CAR-T therapy, but there were no serious treatment-related adverse events.

    • Antigen-Specific Tolerance Induction: This approach aims to induce tolerance to specific antigens associated with autoimmune diseases. By exposing the immune system to these antigens in a controlled manner, researchers aim to re-educate the immune system to tolerate rather than attack the body’s own tissues.

    Complex interaction between immune cells highlighting advanced biotechnology treatments for autoimmune diseases.

    Marin Biologic Laboratories offers a variety of cell-based assays and antibody assays to advance your drug development.  These include

    • Mixed Lymphocyte Reaction (MLR), the classic assay to detect if a cellular component is foreign to an individual’s immune system and will trigger a cytotoxic response. It was commonly used to predict a potential graft rejection. It is often used to determine if a cell transplant treatment is safe in an allogeneic patient, one with different genes than the source of the cells.
    • Enzyme Linked ImmunoSorbant Assay (ELISA) measures cytokines and other proteins with exquisite specificity and sensitivity in complex matrices such as blood and serum.
    • Quantitative Polymerase Chain Reaction (qPCR). The Reverse Transcription (RT) variety measures gene expression, the messenger RNA from activated genes that may be turned on appropriately or inappropriately.