IL-12 (Interleukin-12)

Biology and Diseases

Interleukin-12 (IL-12) is a cytokine expressed by T-cells and natural killer cells in response to the presence of microbial agents. Increased expression of IL-12 drives a positive feedback loop, which generates more T-cells and natural killer cells, along with other immuno-regulatory cytokines such as IFN-γ, IL-10 and TNFα. Although IL-12 is an important initiator of cell-mediated immunity, its pro-inflammatory effects can be deleterious. Over production of this cytokine has been implicated in several autoimmune disorders such as inflammatory bowel disease, psoriasis, autoimmune uveitis and Crohn’s disease.

Therapies

The ability to escalate and strengthen the immune response makes IL-12 an important immunostimulant therapy for infectious diseases and metastatic cancers. In animal models, IL-12 has exhibited antitumor activity against kidney, colon, lung, and ovarian cancer. IL-12 is also being investigated as an adjuvant in ongoing phase I/II clinical trials for improving the efficacy of an HIV vaccine, and in a stage IV clinical trial for a breast cancer vaccine. Furthermore, IL-12 has become an attractive target for therapeutic intervention because of its role in promoting autoimmunity. In this respect, an anti-IL-12/ IL-23 agent (ABT-874) for treating psoriasis and Crohn’s disease has shown positive phase II results.

Unmet Need

The extensive role of IL-12 as a key immuno-modulator makes quantification of circulating IL-12 in plasma important for the development of diagnostic assays for autoimmune disorders, infectious diseases, and cancer. Current ELISA technology is unable to quantify the full range of IL-12 concentrations in healthy patients, limiting its usefulness as a disease marker for cancer, inflammation, and as a surrogate marker for IL-12 targeted therapies. This stresses the need for an immunoassay with greater sensitivity and precision to establish baseline concentrations in normal subjects and detect discreet concentration changes during disease progression.

Singulex Answer

The Singulex IL-12 Assay, optimized for use on the Erenna System, can detect plasma IL-12 over a broad dynamic range. The assay has an LLoQ of 0.06 pg/mL and a reading range of 0.04-2000 pg/mL, which establishes baseline IL-12 concentrations in healthy subjects and detects subtle concentration changes during disease onset or after therapeutic intervention.

This assay will allow investigators to:

1. Measure the efficacy and dosing of anti-IL-12 therapies designed to interfere with autoimmune disorders such as psoriasis and Crohn’s disease.

2. Design robust clinical and preclinical studies when IL-12 concentration is used as a therapeutic endpoint to develop HIV and breast cancer vaccines.

3. Understand how IL-12 concentrations change in patients as they transition from a healthy to diseased state.

Application Note

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