Re-engineering immune cells offers treatment for lupus

By Lauren Davis
Thursday, 08 February, 2024

Re-engineering immune cells offers treatment for lupus

A research team led by Monash University has figured out how to fix a defect that causes lupus — a debilitating autoimmune disease with no cure and limited treatments — by reprogramming the defective cells of lupus patients with protective molecules from healthy people. It is hoped that the new method, described in the journal Nature Communications, can also be adapted for other autoimmune diseases such as diabetes, rheumatoid arthritis and multiple sclerosis.

So-called ‘regulatory T cells’ (Tregs) are supposed to prevent the immune system from attacking the body — but people with lupus, also known as systemic lupus erythematosus (SLE), often have fewer Tregs or their Tregs do not work properly, so their antibodies mistakenly target many of their own proteins, including one called Smith. Treatment options are limited, and drugs that suppress the immune system, like steroids, can cause harmful side effects.

Associate Professor Joshua Ooi, who heads Monash’s Regulatory T Cell Therapies Group, and colleagues re-engineered Tregs from SLE patients to restore their ability to suppress the overactive immune system and thus protect the Smith protein. They achieved this by identifying specific protective molecules in healthy people and reprogramming the ineffective lupus patient Tregs based on these protective properties. Blood cells are taken from the lupus patient, modified in the lab to restore the protective effect and then put back.

When tested in cells from people with SLE, the Smith-specific Tregs reduced inflammatory molecules called cytokines, which are typically high in individuals with lupus nephritis. In a mouse model of lupus nephritis, the Tregs reduced disease severity and proteinuria (high levels of protein in the urine) and prevented kidney damage, highlighting their therapeutic potential.

“We showed the effectiveness of this approach using human lupus patient cells, both in the test tube and in an experimental model of lupus kidney inflammation,” said Ooi, who is co-senior author on the new study.

“We were able to completely arrest the development of lupus kidney disease, without the use of the usual non-specific and harmful immunosuppressant drugs. It’s like a reset of the abnormal immune system back to a healthy state — kind of like a major software upgrade. That it uses the patient’s own cells is a very special part of this.”

Co-senior author Professor Eric Morand, who is Dean of Monash’s Sub Faculty of Clinical & Molecular Medicine and founder of the Monash Lupus Clinic, said the research team is now designing clinical trials expected to start in 2026 to investigate whether this method could be a long-term cure for people with lupus.

“The ability to target, specifically, the disease-causing immune defect, without the need to suppress the entire immune system, is a game changer,” he said. “Even if the effects are only medium term, we are confident the treatment can be easily repeated as needed.”

Co-first author Dr Rachel Cheong, a former PhD candidate at Monash’s Centre for Inflammatory Disease, is confident the new method can be developed for up to 100 other autoimmune diseases such as diabetes, rheumatoid arthritis, multiple sclerosis, Sjögren’s syndrome, scleroderma and myasthenia gravis.

“The great thing is that because the treatment is very specific, it doesn’t harm the rest of the immune system,” she said. “However, this means that the treatment needs to be carefully developed disease by disease, as each one is distinct.”

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