In neurologic autoimmune diseases, the body’s own immune cells (B and T cells) attack the body’s own nervous system (the brain, spinal cord, peripheral nervous or the neuromuscular junction). Two of the more common neuroimmunologic diseases include multiple sclerosis (MS) and Myasthenia Gravis (MG). In MS and MG, therapies that target B cells can be effective for some patients but are not a cure and some patients suffer from side effects.
There is current excitement about cell-based therapies (such as B cell-targeting chimeric antigen receptor T cells, abbreviated as CAR T cells.) B-cells play a leading role in producing antibodies and autoantibodies (which are directed against the patient’s own body). They also work with T-cells by presenting proteins to trigger a T-cell response (working as antigen-presenting cells or APC’s).
CAR T cell therapy was first developed to treat patients with blood cancers. CAR is a combination of different parts of different antibodies-something that does not exist in nature. Cells containing CAR elicit a strong immune response from the patients’ own T cells which are modified and then infused back into patients. These CAR-T cells recognize and kill the target cells. They were first used against CD19 cells, which is the target in many MS therapies. CAR T cell therapy is ideal for fighting neuroimmunologic disease like MG and MS because it crosses the blood-brain barrier, killing the B cells in the tissues affected by the disorder. CAR T cell therapy is believed safe because it doesn’t affect immature B cells in the bone marrow or mature (plasma) cells needed to produce antibodies that combat infection and tumor cells.
While MS and MG are the diseases CAR T is being studied most in, other neuroimmunologic diseases that may someday be treated with this therapy include autoimmune encephalitis, stiff person syndrome, neuromyelitis optica, some forms of transverse myelitis, Chronic Inflammatory Demyelinating Peripheral Neuropathy (CIDP) and others.
The side effects are being studies closely. Currently we are aware of septic-like symptoms when a patient has fever, chills and drop in blood pressure. These side effects can be controlled with steroid and other treatments. Patients treated with CAR T can also develop a neurotoxicity called ICANS which manifests in different ways, including reduced cognitive function. Treatment-related mortality is thought to be between 2 and 4 percent. Because it can take 4-6 weeks to create the CAR T cell product, faster production protocols are being developed and even more of an “off the shelf is approach”.
Because these cells are tailor-made, we have to wait 4 to 6 weeks until we receive the CAR T cell product. This can pose an issue since those patients are in need of rapid intervention because conventional treatment is not working. And there are strategies now to use 24-, 48-hour production protocols or even go to allogenic cells which is similar to an off the shelf approach.
We have over 20 effective approved drugs for MS, so why CAR T and several new ones for MG. So what is the rationale for use of autologous CAR T cells in MS and myasthenia gravis? Because, what we have is not good enough for everyone. Some patients show inadequate disease control, some have infections and some have disease progression for which current effective treatment does not exist. The story is similar in MG. There have been stunning advances over the last decade in MG, but about 10 to 15% of these patients are still refractory. Either they don’t respond to the approved drugs, or they have to halt it because of the side effects. One plausible explanation for why current therapy isn’t sufficient is that they work peripherally, not in the central nervous system.
A big part of the answer, for example, on the MS side, is that while we have medications given either intravenously or subcutaneously that can recognize the CD20 glycoprotein on the surface of B cells, again, sparing the marrow, sparing the terminal plasma cells that produce antibodies, these medications work peripherally and have difficulty crossing the blood-brain barrier..
BeCare Link’s MS and General Neuro Apps can help to monitor your disease progression and your response to widely available therapies. If those therapies are failing you, you may choose to find a CAR T study, empowering yourself and helping yourself and others find a better future. .