CAR T Cell Therapy for Lupus

The immune system is made up of different types of cells, which have different roles in protecting the body from infection. One type of immune cell called a B cell creates antibodies that attack bacteria, viruses, and fungi that cause harm to the body.

As a natural part of this process, some antibodies might target the person’s own tissue instead. These are called autoantibodies. In people with lupus, B cells become dysfunctional and produce too many autoantibodies that cause inflammation in healthy tissue. This inflammation is what leads to lupus symptoms. When the symptoms and inflammation are not brought under control, they can cause organ damage.

How does CAR T cell therapy work?

Like other cell therapies, CAR T cell therapy uses a modified cell either from the patient or from a donor to impact the way a person’s immune system functions. In this case, the modified cell is a type of immune cell called a T cell.

In the most common approach to CAR T cell therapy, T cells are removed from the blood of the patient or from a donor and modified in the laboratory using an engineered protein called a chimeric antigen receptor (CAR) which targets B cells. Once these cells are evaluated for quality and consistency, they are infused into a lupus patient.

Inside the body, CAR T cells grow and expand until there are enough of them to impact how the immune system functions. These CAR T cells then work to greatly reduce the number of B cells throughout the body, lowering overall immune system activity. CAR T cell therapy is a promising approach to treatment that might have the potential to put lupus into remission for long periods for some patients. However, it is very early in the research process and there is much more work that needs to be done to evaluate these treatments. 

What do we know about CAR T cell therapy for lupus?

In 2014, scientists at the University of Pennsylvania developed CAR T cell therapy to treat cancer and now it represents a standard therapy for some kinds of blood and bone marrow cancers. Early studies for CAR T cell therapy for lupus have been promising, but there is not yet enough information to prove that CAR T cell therapy is effective for people with lupus.

One study in 8 patients from Germany with SLE showed remission in some participants up to 3 years after the initial administration of CAR T cell therapy.¹ In the U.S., early results from one company’s clinical trial showed that patients were able to reduce the need for additional therapy or were able to do away with it altogether for some amount of time. In this trial, 7 lupus nephritis patients who were taking 5-10 medications to control their disease were treated with CAR T cell therapy at a baseline dose of 50 million cells (3 patients) or 100 million cells (4 patients). Patients treated with the higher dose improved with minimal addition of immunosuppressive therapy. However, 1 patient flared at 6 months after infusion.²

Most CAR T cell treatments include the use of chemotherapy at the start of treatment. It is not yet clear whether the outcomes being seen are due to the CAR T cells or chemotherapy. However, early reports suggest that some patients have been doing well for longer than would be expected with just the chemotherapy.

It is important to note that so far CAR T cell therapy studies for lupus have been small, with only a few participants. Moreover, patients in earlier studies were not enrolled in a traditional clinical trial. Additionally, these studies do not use a comparison group so the degree of effectiveness of cannot be objectively known.

Current CAR T cell therapy clinical trials are only open to people with refractory illness, meaning their lupus has not responded to standard of care immunosuppressive therapy or biologics. This is because there is potential for significant and serious side effects from this treatment. 

What is a CAR T cell therapy clinical trial like? 

A CAR T cell therapy clinical trial is conducted by a multidisciplinary care team that oversees the preparation, administration, and follow up of the therapy. The clinical trial care team consists of different types of doctors, including:

• A rheumatologist that specializes in treating autoimmune diseases like lupus. 
• An oncologist or hematologist specializing in CAR T cell therapy, who is closely involved in the preparation, administration, and monitoring of the therapy. 
• A neurologist may help address neurological side effects, which can occur during treatment. 
• A nephrologist helps manage kidney complications, since CAR T cell therapy can cause side effects in the kidneys.

Before you qualify for a clinical trial your care team and the trial care team will need to make sure it’s a good fit for you. They’ll check several factors, including your overall health and organ function. It's important to meet certain criteria for your heart, lungs, liver, and kidneys.

Your doctors may also take your age into account, depending on the specific clinical trial. They’ll also consider your living situation, as it is recommended to have a caregiver to be with you through the treatment and follow-up. Where you live may also play a role, as CAR T cell trial participants must be able to remain close to the treatment center for several weeks after receiving the therapy.

Participating in a CAR T cell therapy clinical trial is a 4-step process:

1.  Collection 

Your care team will collect T cells from either you or a donor through a process called apheresis. During apheresis blood is taken from one arm and put through a cell separator to separate the T cells from red blood cells. Blood is then put back into the body through the other arm. The T cells are sent to a lab to be modified using the CAR protein, which can take several weeks. The process takes place over a few hours and does not require staying overnight at the hospital. Prior to collection most clinical trials require patients to minimize or stop their current lupus medications.

2. Preparation

The next step prepares your body to receive the CAR T cells by using chemotherapy to temporarily reduce the number of immune cells in the body. This is called lymphodepletion. It creates a more favorable environment for the CAR T cells to expand and function effectively. By reducing the number of immune cells, the body is less likely to reject the new cells, allowing the therapeutic CAR T cells to target the disease more effectively.

Lymphodepletion requires several days of chemotherapy, and you may have to stay in the hospital. Each person’s experience will be different based on what is best for them and which clinical trial they are taking part in.

Chemotherapy has been used widely for severe lupus and is known to be very effective for lupus. In this case, chemotherapy is being given to help the CAR T cell therapy be effective. However, one “side effect” is that it may immediately have significant beneficial effects on lupus disease activity.

3. Infusion

When you are ready, you will receive your personalized CAR T cells in one infusion. The process usually takes about an hour. From there, the CAR T cells may expand and travel throughout the body to find and subdue the target cells.

At first, you probably won’t feel anything. But the possible complications and side effects from CAR T cell therapy can be very serious, so your care team will monitor you closely for the first few weeks, often during a prolonged hospital admission.

4. Follow up

The time you need to spend in the hospital will vary based on your situation. In general, you will need to stay close to your treatment center for at least four weeks but may return home when your doctor says it is safe to do so. If side effects develop after returning home, you may need to return to the hospital. Friends and family that help with your care will also play a critical role in helping monitor for potential side effects.

Your care team will continue to follow up via phone calls and in-person appointments to assess whether the CAR T cell therapy is working and to watch for side effects. You will see your doctor for ongoing follow-up after treatment, sometimes for years, as mandated by the Food and Drug Administration (FDA), though the frequency of follow-ups may vary and are determined by the doctor.

What are the potential side effects?

Your care team will monitor you for side effects of the treatment. Because CAR T cell therapy has only been studied in a small number of people with lupus, we don’t know all the potential complications of the treatment. Patients will be monitored for infections due to the immunosuppressive nature of lymphodepleting chemotherapy and the CAR T treatment.  They must also be monitored closely for worsening of underlying lupus when previous medications are minimized prior to the clinical trial treatments. In people who have received CAR T cell therapy for other diseases, there are two particularly challenging side effects.

Cytokine Release Syndrome (CRS) is a systemic inflammatory response that can happen in the first few days to several weeks after a patient’s CAR T cells are infused into their body. CRS can cause fever, confusion, fatigue, and nausea, among other symptoms.

Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS) is damage to the brain or peripheral nervous system that can be caused by the engineered cells. ICANS can occur right after cytokine release syndrome or several weeks later. Some ICANS symptoms are confusion, trouble staying awake or walking, shaking, and seizure.

Although these side effects are serious, there are effective treatments and most people fully recover. It isn’t known how common or severe these syndromes will be in patients with lupus, but this is currently being studied.