CAR T-cell therapy: A viable option for myositis treatment?

July 23, 2024July 23, 2024 Category: Research Breakthroughs

Chimeric antigen receptor T-cell (CAR T-cell) therapy is a process developed to treat certain forms of cancers, especially blood cancers like leukemia and lymphoma. Recently, however, researchers have started exploring its use for autoimmune diseases, including idiopathic inflammatory myositis (IIM). This application is still experimental and not yet available for myositis outside of research studies, but we’re excited about the potential of this cutting-edge technology.

Overview

Current CAR T-cell therapy involves taking a patient’s own T-cells (a type of immune cell) and modifying them to better fight cancer cells. These modified T-cells, called CAR T-cells, can recognize and kill cancer cells.

The CAR T process involves several steps. First, T-cells are collected from the patient’s blood. Next these cells are engineered in a lab to attach special protein receptors (CARs) to the T-cells that can then bind to target cells (cancer cells in the case of malignancies and most often antibody producing B-cells in autoimmune diseases). These modified T-cells are then grown in large numbers and reinfused back into the patient’s body, where they can attack the cancer cells and disable them.

Before reinfusing these reengineered T-cells, patients may need to undergo preconditioning treatment with a combination of chemotherapy agents. This allows for better incorporation of CAR T-cells into the immune system.

CAR T-cell therapy and myositis

With autoimmune diseases, including myositis, the idea is to “reset” the immune system by modifying T-cells to attack the immune cells that are causing muscle inflammation. This is similar to the way CAR T-cells target cancer cells. Scientists are now testing this process to see if it is safe and effective as a treatment for myositis.

One of the challenges in this process is finding the right target. It’s difficult to know what specific markers on the immune cells are causing the inflammation. Unlike cancer cells, which often have unique markers, the immune cells in autoimmune diseases are the body’s own cells and can vary widely depending on the form of myositis and the autoantibody status. The current strategy is to target autoantibodies producing B-cells by aiming for a certain protein—CD19 or BCMA—that sits on the cell surface.

CAR T-cell therapy can also cause serious side effects, such as cytokine release syndrome (CRS). CRS happens when your immune system overreacts, sending out more immune cells than necessary. CAR T therapy can sometimes also cause damage to the nervous system.  

Research

CAR T-cell therapy is still in the research phase as a treatment for myositis. This will take some time before this therapy, if proven safe and effective, becomes a treatment option for myositis patients.

Several research centers and multiple pharmaceutical companies are currently exploring the use of CAR T-cell therapy to treat myositis. One significant study involves CD19 CAR T-cell therapy, which has shown promise in treating various autoimmune diseases, including myositis. This research is still in the early stages but has produced some promising results.

Cabaletta Bio, for example, is conducting trials with their CD19-directed CAR T-cell therapy, CABA-201, for patients with myositis and lupus. Early findings suggest that this therapy can effectively deplete B-cells, which are involved in the autoimmune response, potentially leading to remission without the need for ongoing immunosuppressive medication.

The good news is, researchers have observed that the effectiveness of CAR T-cell therapy is consistent in different patients, regardless of what previous treatments they might have had. Patients also seem to tolerate the treatment fairly well and are able to manage side effects.

CAR T-cell therapy has potential for treating autoimmune diseases like myositis, but it is still in the early stages of research. TMA is excited by this innovative new approach to treatment for autoimmune diseases and are eagerly working together with the research community to advance the science that may one day achieve our vision of a world without myositis!