TARGETING AUTOIMMUNE DISEASE AT ITS ROOT
As part of the innate immune system, natural killer (NK) cells play a vital role as the body’s first line of defense against dysfunctional, diseased or otherwise abnormal cells. NK cells patrol the body to identify and kill abnormal cells that could be harmful to healthy tissue. They do this by recognizing markers of stress on the surface of problematic cells, independent of the antigens they display. This allows NK cells to target a wider range of disease-causing cells than T cells, which are white blood cells that only target cells that display specific antigens, and makes them well suited for addressing the pathogenic B cells that are at the root of many autoimmune diseases. To explore whether this natural ability can be enhanced, Nkarta’s cell therapy candidate adds a chimeric antigen receptor (CAR) to target B cells and a membrane-bound form of IL-15 to enhance activity and persistence.
Eliminating Pathogenic B cells
B cells have three main functions: producing autoantibodies, presenting antigens to other cells of the immune system, and secreting cytokines. All three of these functions play a role in the development of autoimmune disease. Normal B cells help the body fight infection by producing antibodies that target antigens from viruses, bacteria and other pathogens. Abnormal B cells are considered a key contributor to many autoimmune diseases, because they secrete autoantibodies that can work against the patient’s own body to cause the immune system to attack healthy tissue. Clinical studies have shown that deep depletion of abnormal B cells may address autoimmune disease by eliminating the offending B cells that produce these autoantibodies, allowing normal B cells to replenish. This “immune reset” could offer patients the possibility of achieving long-lasting remission.
Nkarta’s investigational CAR NK cell program, NKX019, is engineered with a CAR targeting CD19 found on most B cells. By eliminating pathogenic B cells and initiating this reset, our cells have the potential to transform the standard of care for patients with B cell-mediated autoimmune diseases such as lupus nephritis (LN), systemic lupus erythematosus (SLE), systemic sclerosis (SSc or scleroderma), idiopathic inflammatory myopathy (IIM or myositis), ANCA-associated vasculitis (AaV or polyangiitis), primary membranous nephropathy (pMN) and other autoimmune diseases.
What is systemic lupus erythematosus?
Systemic lupus erythematosus (SLE) is an autoimmune disease that causes the body’s immune system to attack its own tissues. The dysregulated immune system produces autoantibodies that can affect various organs, including the skin, joints, kidneys, heart and brain.
Lupus nephritis is a severe manifestation of SLE that occurs when the immune system mistakenly attacks the kidneys, leading to inflammation and potential organ damage and kidney failure.
What is primary membranous nephropathy?
Primary membranous nephropathy (pMN) is an autoimmune disease that causes the body’s immune system to attack the filters of the kidneys. Unlike lupus nephritis, pMN arises on its own and is not caused by SLE.
What are idiopathic inflammatory myopathies?
Idiopathic inflammatory myopathies (IIM or myositis) are a group of autoimmune conditions characterized by inflammation of muscle and other organ systems often resulting in organ failure.
What is ANCA associated vasculitis?
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an umbrella term for a group of rare autoimmune conditions, such as polyangiitis, that cause inflammation of blood vessels.
What is systemic sclerosis?
Systemic sclerosis (SSc) is a chronic disease of the connective tissue where its rapid growth causes scarring of skin and internal organs.
