Immunotherapy removes MS-like disease cells in mice

Since its introduction in 2017, the cancer treatment known as CAR-T has transformed the way some blood malignancies are treated. Immune cells that have been genetically modified are used in the immunotherapy to target and kill cancer cells.

Researchers at Washington University School of Medicine in St. Louis have now demonstrated that the same method can be used to eradicate undesirable cells that cause autoimmunity by analyzing mice with an autoimmune illness comparable to multiple sclerosis (MS). The research, which is published online in Science Immunology, extends the usefulness of immunotherapy to a group of frequently crippling and challenging-to-treat disorders.

According to co-senior author Chyi-Song Hsieh, MD, PhD, the Alan A. and Edith L. Wolff Professor of Rheumatology and a professor of medicine and pathology & immunology, “We were able to use CAR-T cells to eliminate just the immune cells that are causing the autoimmunity and not other immune cells you might need to protect against viruses or other infections.” Our CAR-T cells successfully treated mice with an MS-like condition.

T cells, essential components of the immune system and the body’s defensive mechanism, are at the core of CAR-T Immunotherapy . T cells coordinate an immune attack and kill foreign organisms as well as infected or malignant cells in response to threats including bacteria, viruses, and cancerous cells.

But occasionally, T cells misidentify healthy cells as pathogens and launch an attack on the body’s own cells and tissues, leading to an autoimmune illness. Rogue T cells, which cause the loss of myelin, the protective covering over nerves, are a hallmark of MS. People start to experience symptoms like weariness, pain, tingling, vision issues, and loss of coordination when myelin is destroyed and communication between the brain and spinal cord and the rest of the body becomes unreliable. Immunosuppressive medications can stop renegade T cells from damaging themselves, but they also suppress healthy T cells, increasing the risk of serious infections.

In CAR-T cancer immunotherapy , doctors take a patient’s own T cells, modify them to recognize and aggressively attack that patient’s particular cancer, and then reintroduce them into the body on a mission to find and eliminate it. Inspired by this strategy, the researchers set out to develop CAR-T cells that are able to locate and eliminate the renegade T cells responsible for MS. The goal was to create CAR-T cells that would work like an internal affairs office for a police force, weeding out the bad T cells while leaving the good ones in place to protect the body.

According to co-senior author Gregory F. Wu, MD, PhD, an associate professor of neurology and pathology & immunology, “MS can seriously degrade your quality of life, and while existing immunotherapy slow down the course of the disease, they don’t cure it and have adverse effects.” “I firmly believe that this is a curable condition, and CAR-T cells may pave the path for far more effective therapies.”

The research team also includes Takeshi Egawa, MD, PhD, an associate professor of pathology and immunology, and Nathan Singh, MD, an assistant professor of medicine, as co-authors in addition to Hsieh and Wu.

The researchers first created some bait. By fusing a piece of a protein found in myelin with a protein that stimulates T cells, they created a molecule. Only myelin-targeting T lymphocytes, or “bad apples,” would react to this chemical combination protein that stimulates T cells, they created a molecule. Only myelin-targeting T lymphocytes, or “bad apples,” would react to this chemical combination. Then, they attached the bait molecule to killer T cells, a subset of T cells. The killer T cells would eradicate any rogue T cells that succumbed to the bait.

At least, that was the thought. The researchers tested it on mice with a condition similar to MS to see if it was effective. By administering the modified CAR-T cells to these mice, disease was averted in those who hadn’t yet had symptoms, while disease symptoms were lessened in those who had previously experienced neurological damage.

To get better treatment outcomes, Hsieh added, “We’re working on enhancing the CAR-T cells to get them to kill more effectively and survive longer.” We can’t predict who will develop MS or when, so preventing the disease in humans isn’t possible. However, we can treat it, and the CAR-T method seems highly promising.

The genius of the CAR-T strategy is that different rogue immune cells can be targeted by killer T cells to treat various diseases by changing the protein fragment in the bait molecule.

Myelin oligodendrocyte glycoprotein (MOG) antibody disease is a rare condition that, according to Wu, affects people and is very similar to multiple sclerosis (MS). “In contrast to MS, which is complex, we are completely aware of the target in MOG antibody illness.” I wish there was a way to just eradicate these self-reactive cells for my patients, but there isn’t. “Now, our goal is to develop CAR-T cells from the patient’s own immune cells to eradicate those self-reactive T cells.”