CAR T Cell Therapy | Using Immune System Cells to Fight MS

Multiple Sclerosis Disease Course

Multiple sclerosis is a chronic disease that affects the central nervous system – the brain and spinal cord – driven by the body’s own immune system.

In MS, the immune system begins to recognize normal cells and tissues in the central nervous system as if they are foreign invaders for reasons that are not completely clear. Normally, our immune system leaves the body’s cells and tissues alone and only attacks invaders such as bacteria, viruses, and parasites. However, the immune system can malfunction and produce inflammation and damage to normal cells and tissues. In MS, various immune cells either directly damage or signal other cells to damage the insulation around nerve fibers, known as myelin, the cells that make myelin, and the nerve fibers that carry messages inside the central nervous system. Over time, more damage causes progression of the disease with worsening symptoms.

Current MS Treatments

There are over 20 FDA-approved medications, known as disease-modifying therapies (DMTs) that are FDA-approved to treat MS. These medications have been developed to modify or suppress certain cells and processes of the immune system and thereby turn down inflammation, reduce damage, and delay progression of disability. There are different classes of MS DMTs – with each class addressing the immune system in a different way – all to get to the same effect of less MS disease activity.

The current MS DMTs work – but they are not a cure, and they do not work for everyone – particularly people with non-active secondary progressive MS and those with primary progressive MS. In these cases, there is still the real possibility that the disease will worsen over time, even while on a DMT. Because of this, researchers continue to identify new targets and design new medications to better treat the MS disease process.

Emerging Cell Based Therapies

Cell-based therapies have emerged as potentially effective treatments for MS. Stem cell transplantation, using the body’s own stem cells, known as autologous hematopoietic stem cell transplantation (AHSCT) has been used successfully in people highly active MS who have not responded to current MS DMTs. However, AHSCT is a complicated treatment, carries risks, and is not available everywhere. Recently, another type of cell therapy, known as chimeric antigen receptor T cell therapy, or CAR-T cell therapy, has emerged as a possible treatment for MS that may be less complicated than AHSCT.  

While new to the MS community, CAR-T cell therapy has been FDA-approved for certain types of blood cancer since 2017. CAR T cell therapy outcomes in the treatment of blood cancers have been quite good, and researchers are now evaluating the potential benefit of this therapy in autoimmune conditions, including MS.  

How Does CAR-T Cell Therapy Work?

Cytotoxic (cell killer) T-cells are like hunters – they roam the body looking for things that do not belong.  Cancer cells, for example, express proteins that can be recognized by T cells. Once recognized, T cells jump into action to kill off the cancer cells. But sometimes, the cancer cells figure out a way to get past the T cells and cause illness.   

Cancer researchers found a way amplify T-cell activity and improve the T cell’s ability to find and destroy cancer cells.  The therapy involves the collection of T cells from the blood and reengineering them in the laboratory, so they produce a specific receptor on their surface – known as a chimeric antigen receptor or CAR. The CAR allows the T cell to rapidly and efficiently identify cancer cells and then destroy them. The results of CAR-T cell therapy in blood cancers has been very positive. 

How Could CAR-T Cell Therapy Be Used to Treat MS?

In MS, the fight is not with cancer cells. The fight is with the body’s own immune system – where cells of the immune system attack cells and tissues in the central nervous system. As noted above, there are numerous immune system cells involved in MS. One is the B cell, a type of lymphocyte that has multiple functions in MS that ultimately result in inflammation and damage in the central nervous system. Several of the FDA-approved DMTs target B cells, and by reducing the number of B cells in circulation, these treatments limit new MS activity in the central nervous system.  

Researchers believe CAR T therapy could help cytotoxic T cells rapidly identify and eliminate B cells with a certain protein on their surface called CD-19. It has been recently identified that an important part of MS damage is an ongoing “smoldering” process where immune cells, such as B cells, and certain central nervous system cells cause damage.  CAR-T cells have the ability to enter the central nervous system, and they may potentially be more effective than medicine that can only work outside the central nervous system.  

Studies of CAR-T cell therapy in animal models of MS have been positive. Now clinical trials in people with MS are getting underway – for primary-progressive and secondary-progressive MS. Currently, there is only one FDA-approved treatment for primary-progressive MS and FDA approvals that include secondary-progressive MS are only for active secondary progressive MS, a subset of all those with secondary progressive MS. CAR-T cell therapy may be able to address significant unmet need for people who live with progressive forms of MS. 

Your Call to Action

CAR-T cell therapy holds significant hope in MS and has the potential to address the unmet need in progressive MS. It is currently in clinical trials to establish benefits as well as side effects and risks. Now is the time to speak with your MS care provider to get clarification on the treatment itself and to learn if a clinical trial might be right for you. For more information on CAR-T cell therapy for MS please visit clinicaltrials.gov.