CAR-T Therapy May Treat Conditions Other Than Blood Cancers, Research Shows

CAR-T therapy is one of the newest and buzziest treatments for leukemia and lymphoma, hailed a potential cancer “cure” earlier this year for its long-term ability to keep patients cancer-free.

The FDA approved the first CAR-T therapy in 2017, and early outcomes show that it has the potential to be effective and well-tolerated for many individuals who do not respond to existing traditional treatments.

The question is: What else can CAR-T do? Ongoing research shows the technology has the potential to expand to other conditions—like tumorous cancers and noncancerous diseases.

What Is CAR-T?

For patients with certain types of blood cancers that do not respond to chemotherapy or recur after treatment, chimeric antigen receptor T-cell therapy (CAR-T) offers another possible treatment course.

“The immune system is great at patrolling cancers,” Lee Greenberger, PhD, Chief Scientific Officer for the Leukemia and Lymphoma Society (LLS), told Verywell. “As you get older, unfortunately, the immune system becomes less effective. We are replacing immunotherapy for what nature does.”

T cells, a type of white blood cell, are one of the body’s primary defenses against infection and cancer. CAR-T therapy transforms a person’s native T cells into cancer fighters. It relies on four steps:

• A blood draw
• A process called apheresis to separate red blood cells, white blood cells, platelets, and plasma
• Genetic engineering in a lab to add a protein to T cells
• An infusion

Because the genetically altered T cells can live in the body and remain active for years, CAR-T is a one-and-done approach to fighting cancer. Patients do not need to repeat treatments as they do with chemotherapy.

CAR-T Is Currently Approved to Treat Leukemia and Lymphoma

As of March 2022, six CAR-T therapies have FDA approval to treat cancers that recur after treatment or do not respond to other therapies:

• Kymriah (Tisagenlecleucel): B-cell non-Hodgkin lymphoma and follicular lymphoma in adults; acute lymphoblastic leukemia (ALL) in children and adults over 25 years of age
• Yescarta (Axicabtagene ciloleucel): B-cell non-Hodgkin lymphoma and follicular lymphoma in adults
• Tecartus (Brexucabtagene autoleucel): multiple mantle cell lymphoma and acute lymphoblastic leukemia (ALL) in adults
• Breyanzi (Lisocabtagene maraleucel): B-cell non-Hodgkin lymphoma in adults
• Abecma (Idecabtagene vicleucel): multiple myeloma in adults
• Carvykti (Ciltacabtagene autoleucel): multiple myeloma in adults

Promising Research for Other Blood Cancers

Current CAR-T therapies program T cells to attach to one of two markers found on many blood cancer cells: CD-19 or BCMA. However, other markers also play a role in many blood cancers.

Researchers at Fred Hutchinson Cancer Center have been studying an experimental CAR-T therapy called MB-106 that targets a blood cancer marker called CD20. In addition to treating patients with B-cell non-Hodgkin lymphoma like some of the FDA-approved CAR-T drugs, MB-106 may also be used to treat chronic lymphocytic leukemia (CLL).

“Each CAR-T construct has a target on a lymphoma cell that it goes for,” Mazyar Shadman, MD, MPh, associate professor of the clinical research division at Fred Hutch Cancer Center, told Verywell. “We’re aiming for a different target than other CAR therapies, which gives us another way of targeting and attacking lymphoma cells.”

Targeting alternative markers may also be useful when existing CAR-T treatments fail. Shadman noted only 30% to 40% of patients are cured from current CAR-T treatments.

“[MB-106] covers a space that is considered to be an unmet need in lymphoma treatment, including patients who have already received CD-19-directed CAR T,” he said.

Shadman said his research team is particularly hopeful that MB-106 will prove effective at treating Waldenstrom macroglobulinemia (WM), a rare subtype of non-Hodgkin lymphoma.

Next Stop: Treating Other Cancers

LLS’s Greenberger said it’s possible CAR-T can be used to treat cancer beyond leukemia and lymphoma, which are blood cancers.

“I suspect that what we learn about blood cancers will also apply to solid tumors,” he said. For example, a recent study suggests that some breast cancers might respond to CAR-T therapy.

While all currently FDA-approved CAR therapies modify the T cells (and are thus known as CAR-T), some CAR therapies in development will employ other cells within the immune system. This includes natural killer (NK) cells and macrophages, expanding the potential reach of the treatment.

CAR-T May Have Uses Beyond Cancer, Too

CAR-T therapies may also be an option for some noncancerous illnesses in the future. Right now, researchers are exploring its use across a variety of conditions:

• Graft versus host disease: GVHD is a condition in patients who have undergone bone marrow and stem cell transplants. In GVHD, healthy T cells from the donor attack and destroy the recipient’s non-diseased cells. CAR-T therapy may reprogram the recipient’s T cells not to attack their healthy cells.
• Systemic lupus erythematosus: Targeted CAR-T therapy may alleviate symptoms for lupus patients who have not responded to other treatment options.
• Cardiac disease: Some patients with cardiac fibrosis (scarring of the heart tissue) may be able to regenerate healthy heart tissue with CAR-T therapy.
• Fungal pulmonary aspiration: Many fungi pose minimal risk to healthy individuals, but people with a weakened immune system are at higher risk for developing fungal infections. One fungus, aspergillus, may cause pneumonia if an individual inhales oral secretions into the lungs. However, researchers in one study programmed CAR-T cells to kill off fungal infections in the laboratory.

Will CAR-T Become a First-line Treatment Option?

CAR-T therapy is still in its infancy, and much remains unknown. CAR-T could become the first treatment of choice for some patients in the future, but for the time being, many traditional treatment options remain the gold standard.

“We know the safety profiles of the FDA-approved CAR-T therapies, but nobody should be giving CAR-T for conditions it’s not approved to treat,” Greenberger said. “It will take more time to get current CAR-T therapies approved as first-line treatment. Trials must prove first that these treatments are both efficacious and safe. They are also expensive, so you have to weigh their benefits against the cost of traditional treatment.”

High-quality research takes time, and many CAR-T researchers often work with a limited subject pool.

“Some of the conditions we are studying are so rare it takes a while to get the data we need,” Greenberger said. “But I anticipate that in the next 5 or 10 years, you will see CAR-T move from the third-line course of action to first or second-line treatment.”

In the meantime, researchers are excited to see the potential CAR-T therapies hold for patients.

“Twenty or 30 years ago, we would have said immunotherapy would not work. Now we have a whole arsenal of immunotherapeutics, and their use continues to grow,” said Greenberger. “We’re not done learning—not by a long shot. We’ve still got a lot of ground to cover.”