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Cell therapy hope in treatment of lupus: Researchers

Current treatments include immunosuppressive drugs such as hydroxychloroquine, steroids that target T-cells or antibody-producing B-cells

G.S. Mudur New Delhi Published 17.09.22, 01:55 AM
Representational image.

Representational image. File photo

Medical researchers announced on Thursday their use of an experimental cell therapy to treat an autoimmune disorder called systemic lupus erythematosus, showing drug-free remission for five to 17 months in five patients.

All five patients — four women and one man aged 18 to 24 years — who had difficult-to-treat lupus, showed continuous improvements in symptoms after receiving the so-called chimeric antigen receptor (CAR) T-cell therapy, researchers in Germany said.

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In lupus, antibodies generated by the immune system attack the kidneys, heart, lungs or the skin. Current treatments include immunosuppressive drugs such as hydroxychloroquine, steroids or special drugs that target the immune system’s T-cells or antibody-producing B-cells. But such treatment options are frequently ineffective and no cure is known.

Now, George Schett at the Friedrich Alexander University and his colleagues have treated the five patients — each of whom had treatment-resistant lupus — with engineered CAR T-cells designed to remove antibody-producing B-cells by targeting a protein on their surface.

All the five patients had multi-organ lupus that had affected their heart, kidneys, lungs and joints. Following the CAR T-cell therapy, their destructive antibodies disappeared, their symptoms improved, they were able to stop their conventional immunosuppressive treatment and have remained disease-free for five to 17 months, the researchers said, reporting their observations in the journal Nature Medicine on Thursday.

Since 2017, the US Food and Drug Administration has approved six CAR T-cell therapies approved only for the treatment of certain blood cancers, including lymphomas, some forms of leukaemia and multiple myeloma. Currently available CAR T-cell therapies are tailored for individual

patients.

In 2019 and 2021, research groups in the US and China had shown that CAR T-cell therapy was effective in the treatment of mice designed to function as animal models for lupus. Based on those studies, the German group decided to test the safety and efficacy of the CAR T-cell therapy in lupus patients.

The researchers have cautioned that while their results are encouraging, studies on more patients are necessary to evaluate safety and efficacy. Like other anti-cancer treatments, CAR T-cell therapies have been known to cause severe side effects, including the depletion of antibody-producing cells and infections. A particularly serious side effect is called the “cytokine release syndrome”, in which the infused T-cells flood the bloodstream with cytokines causing dangerously high fever and a drop in blood pressure.

“Currently, the ideal patient profile for CAR T-cell treatment in lupus is not established, and not every patient may respond,” Schett and his colleagues wrote in their paper. “In our study, the patients with multi-organ involvement were resistant to conventional treatments and had limited organ damage.”

But considering that the lupus in the five patients was highly resistant to the immunosuppressive treatments, the results indicate that CAR T-cells can stop the underlying autoimmune processes in lupus.

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