CAR-T's Journey: From Cancer to Lupus Success in Cell Therapy

In recent developments, there is growing interest in the potential of CAR-T cell therapy to treat autoimmune diseases, an innovation traditionally confined to oncology. This is largely due to the effectiveness of CAR-T therapy against B-cell malignancies, as highlighted during a lecture by Dr. Georg Schett at the German National Academy of Sciences Leopoldina. The treatment was applied to a 20-year-old patient with severe systemic lupus erythematosus (SLE) who had exhausted all other treatment options. Her condition included serious symptoms such as endocarditis, pleurisy, arthritis, and elevated urine protein levels, indicating possible kidney failure.

In a bid to improve her prognosis, doctors at the University Hospital Erlangen opted for an experimental CD19 CAR-T cell therapy aimed at the autoreactive B cells causing her illness. Despite concerns about potential severe immune reactions, the treatment yielded remarkable results. Within just 30 days, the patient’s protein levels normalized, and her lupus biomarkers disappeared. The autoreactive B cells attacking her organs were eradicated, and three years later, she remains symptom-free and treatment-free, with non-autoreactive B cells regenerated.

This success story is part of a broader study involving 15 patients treated for lupus, systemic sclerosis, and idiopathic inflammatory myositis. According to Schett, nearly all participants have shown no signs of disease and have not required further treatment. These encouraging outcomes have spurred significant interest from companies such as CRISPR Tx, Kyverna, and Novartis, which are now investing in CAR-T approaches for autoimmune diseases.

Regeneron, known for the monoclonal antibody Dupixent, also expressed enthusiasm about the promising data. Philip Gregory, head of Regeneron Cell Medicines, highlighted the transformative potential of using oncology targets for treating autoimmune conditions like lupus. Supporting this idea, healthcare analyst Dr. Sami Corwin pointed out that academic studies from Germany have shown the possibility of inducing a durable, drug-free remission in severe autoimmune patients through CAR-T therapy.

CAR-T therapy has been a significant player in oncology for over a decade, particularly effective against blood cancers like acute B cell lymphoblastic leukemia and B cell lymphoma. These cancers involve the same immune cells that are autoreactive in lupus, making it logical to apply CAR-T therapy to autoimmune diseases. Dr. Miloš Miljković, Chief Medical Officer at Cartesian, emphasized this overlap, noting that their clinical trials on Descartes-8, an autologous BCMA-directed, mRNA-engineered CAR-T therapy, are targeting the autoimmune disease myasthenia gravis, which has a similar mechanism to lupus but affects the neuromuscular system.

The University Hospital Erlangen’s studies suggest that the same CAR-T protocols used in cancer treatments can be effective for autoimmune diseases. In these studies, patients received the same CAR-T dosage as in a phase 1 trial for B cell lymphoma, experiencing only minor side effects such as fevers and no severe issues like cytokine release syndrome or neurotoxic syndrome.

Despite these promising results, the early studies were limited in size and scope, focusing only on three autoimmune conditions. Future effectiveness will depend on careful disease and patient selection, as well as considerations such as target selection, lymphodepletion, and concurrent medications. Researchers also need strategies for handling relapses, as evidenced by a recent case of disease recurrence managed with a re-exposure to CAR-T cells.

Challenges notwithstanding, the promising results indicate that CAR-T therapy might soon be expanded to other applications. Researchers at the University Hospital Erlangen are exploring its potential in treating conditions like HIV, cardiac fibrosis, hepatitis B, and even cell senescence. 

How to obtain the latest research advancements in the field of biopharmaceuticals?

In the Synapse database, you can keep abreast of the latest research and development advances in drugs, targets, indications, organizations, etc., anywhere and anytime, on a daily or weekly basis. Click on the image below to embark on a brand new journey of drug discovery!