Promising Lupus Therapy May Emerge from 1990s Cancer Treatment, Immune Factor IL-2

Sometimes, looking backward is a good way to go forward. With this in mind, scientists discovered that a cancer drug approved decades ago, based on the immune molecule IL-2, may restore balance to the overactive immune systems of people with systemic lupus erythematosus (SLE).

IL-2, or Interleukin-2, is rarely used in cancer treatment today. But, the researches noted, as an approved drug with a known safety profile, its clinical development as a lupus treatment would be much speedier than usual, meaning it could reach patients within a few years. Their study, “Low-dose interleukin-2 treatment selectively modulates CD4 T cell subsets in patients with systemic lupus erythematosus,” was published in the journal Nature Medicine.

The discovery came from observations that lupus patients often have low levels of the immune cytokine IL-2. This factor is an early signal prompting the production of different kinds of T-cells, and an imbalance between inflammatory types of T-cell and those acting to control inflammation is exactly what is seen in lupus.

In cancer, versions of this factor, produced in the lab, have been used since the early 1990s, but scientists only recently started to test the drug on patients with immune conditions. Researchers at the Monash Biomedicine Discovery Institute in Australia, working with colleagues at the Peking University People’s Hospital in China, studied if low doses of IL-2 had any impact on patients with active lupus disease.

The team recruited 38 patients who did not respond well to standard lupus treatment (NCT02084238). Patients were treated for 12 weeks with low doses of IL-2, and 89.5 percent of them had a four-point drop in the SLE disease activity index — a tool often used to measure disease activity.

“The real promise of this treatment is that it calms the hyperactive immune system through multiple mechanisms, which is very important as this new therapy may be effective for many patients,” Eric Morand, a professor at Monash University, founder of the Asia Pacific Lupus Collaboration, and a study co-author, said in a news release.

Almost all patients could reduce their corticosteroid dose by at least 25 percent, and 67.6 percent reduced to half or less the dose they were taking at study start. Researchers also showed that the treatment acted on all lupus symptoms explored: rash, hair loss, arthritis, fever, and inflammation of serous membranes throughout the body.

Researchers also noted that the treatment shifted the composition of T-cells. A change from predominant inflammatory T-cells to more regulatory T-cells, also called Tregs, was seen in the blood of patients, with inflammatory cells decreasing in numbers.

“The amount we tested for treating lupus is much less than the dose used in treating cancers,” said Di Yu, a professor at Monash Biomedicine Discovery Institute  who led the study together with Zhanguo Li of China.

“We observed the treatment was safe and showed promising results, so there’s reason to believe formal trials could begin almost immediately,” Morand added. “As the drug has been on the market for some time for other diseases, it can be rapidly put into formal trials for lupus treatment right away.”