Potential treatment of rare autoimmune diseases with CAR-T therapy

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Evidence from a small clinical trial suggests that a variant of an immunotherapy for advanced blood cancers known as CAR-T could be used to treat myasthenia gravis, an autoimmune disease of the nervous system. The modified CAR-T therapy used by the scientists (short for chimeric antigen receptor T-cells) offered the potential to reduce symptoms of myasthenia gravis more durably and was well tolerated with no significant adverse effects. The study, published in The Lancet Neurology, was funded by a small business grant from the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health, and sponsored by Cartesian Therapeutics, Gaithersburg, MD.


What is Myasthenia gravis?

Myasthenia gravis is a chronic autoimmune disease most commonly caused by the body’s immune system attacking a protein where nerve cells communicate with muscles.The disease is characterized by muscle weakness that worsens after a period of activity and improves with rest. Current treatments focus on controlling symptoms, primarily muscle weakness.


How did they conduct the study?

In the study, 14 patients with generalized myasthenia gravis received varying doses of a modified CAR-T therapy called Cartesian-08, which targets cells that produce antibodies to myasthenia gravis. The ideal dosage is once a week for 6 weeks. Early data on the effects of the treatment are promising, but more clinical studies are needed to assess the effects of the treatment. Three patients treated with Descartes-08 showed complete or near-complete resolution of symptoms, which persisted for six months after treatment. The other two no longer required chronic intravenous immunoglobulin therapy, which is currently used in some severe cases of MG.


“What we saw with Decartes-08 was a profound, durable response that lasted at least six months after treatment,” said Murat V. Kalayoglu, MD, president and chief executive officer of Cartesian Therapeutics. ” We have now initiated a larger randomized, placebo-controlled study, the first of its kind for engineered adoptive cell therapy.”


CAR-T therapy involves taking a patient’s T cells, a key part of the immune system that recognizes and destroys invading pathogens, and reprogramming them to attack specific targets. In the case of blood cancers, the new target is the cancer itself. With myasthenia gravis, the target is damaged cells that produce damaging antibodies.


Many immunotherapies, including car t cell immunotherapy, carry a risk of serious side effects that, while tolerable in advanced cancer cases, are contraindicated in more chronic diseases such as myasthenia gravis. Normally, T cells are reprogrammed with DNA, which persists inside the cell and is replicated every time the cell divides. This can lead to magnified effects and serious side effects.


To avoid this side effect, Descartes-08 uses messenger RNA (mRNA) instead of DNA to reprogram T cells. Messenger RNA is not replicated when cells divide. The result is a short course of multiple treatments, rather than the single-dose regimen typically used in DNA-programmed CAR-T therapy. The main objective of this trial is to determine the ideal dose of Descartes-08 to effectively relieve symptoms of muscle weakness and minimize side effects.


The Descartes 08 therapy is currently undergoing a larger clinical trial to determine its ability to reduce symptoms of myasthenia gravis. Importantly, the trial will also include a placebo group, an important control to confirm that any observed improvements are due to the treatment and not any unrelated effects.


Background of CAR-T Therapy


What is CAR-T Therapy?

CAR T-cell therapy is a type of immunotherapy in which a patient’s own T cells are modified to recognize and attack cancer. T cells are extracted from the blood of a patient. In the laboratory, the gene for a special receptor that binds to a specific protein on the patient’s cancer cells is then added.


Car t Cell Therapy Process

Collected T cell from the patient

T cell activation

T cell reengineering

T cell multiplied

CAR-T cells infusion

CAR-T cell against recurrence


Car t Structure

The ectodomain, transmembrane domain, and endodomain are the three regions that make up CARs.


What Cancers Can Be Treated with Car t-Cell Therapy?
The US Food and Drug Administration (FDA) has approved CAR T-cell therapies to treat certain lymphomas and leukemias, as well as multiple myeloma.


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