IL-15 (Interleukin-15)

Biology and Diseases

Interleukin-15 (IL-15) is a cytokine that bears structural and biological similarities to IL-2, as both cytokines are triggered by the presence of exogenous bacteria and viruses. Unlike IL-2, which is expressed mainly by activated monocytes, IL-15 is constitutively expressed by a variety of tissues and cell types, including macrophages, dendritic cells, osteoclasts and fibroblasts. IL-15 is known to affect the proliferation of T-, B- and natural killer cells, and initiates the up-regulation of the cytokines GM-CSF and TNFα. The pro-inflammatory properties of IL-15 elicit autoimmune activity and elevated levels of IL-15 have been associated with psoriasis, multiple sclerosis, rheumatoid arthritis and systemic lupus.

Therapies

The pivotal role of IL-15 in escalating the inflammatory response has led to development of IL-15 targeted biologics for a variety of disorders. A human monoclonal antibody against IL-15 (Humax-IL 15/AMG 714) has undergone a successful phase I trial. Also, a mouse monoclonal antibody (Mikβ1) that targets the IL-15 receptor β-subunit has been tested in preclinical and phase I studies for treating patients with T-cell large granular lymphocyte leukemia, however efficacy remains to be shown. In addition, researchers are currently evaluating the safety and immune response of an HIV vaccine with and without IL-15 as a booster adjuvant in a phase I trial.

Unmet Need

IL-15 is a novel cytokine whose involvement in inflammation and autoimmunity has not been fully determined. Studies designed to assess the tolerance and efficacy of IL-15 therapies will offer insight into treating psoriasis, rheumatoid arthritis and Crohn’s disease. This presents a need to accurately quantify IL-15 during preclinical and early phase drug development. It is also imperative to establish baseline concentrations of plasma IL-15, a component essential to determine therapeutic dosing required to bring IL-15 from diseased states down to normal levels.

Singulex Answer

The Singulex IL-15 assay, optimized for use on the Erenna System, provides excellent sensitivity and precision over a broad dynamic range. The assay has an LLoQ of 1.6 pg/mL and a reading range of 0.42-2000 pg/mL, allowing detection of subtle IL-15 concentration changes to be mapped to different stages of disease progression.

This assay will allow investigators to:

1. Measure the efficacy and dosing of anti-IL-15 therapies designed to interfere with autoimmune disorders such as psoriasis, rheumatoid arthritis and Crohn’s disease.

2. Design robust clinical and preclinical studies when IL-15 concentration is used as a therapeutic endpoint in developing HIV vaccines.

3. Understand how IL-15 concentrations change in patients as they transition from a healthy to diseased state.

Application Note

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