Cellular therapy developed for cancer now being tested in autoimmune disease

Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine, has joined with 40 other centers in the U.S. and Europe as a site in one of the first clinical trials testing cellular therapy for autoimmune disease in the U.S.

Although the cellular therapy, which is known as CAR T therapy, was developed for patients with B-cell lymphomas, researchers soon realized that it might have applications beyond cancer as well. 

“The way I see it, we are at the nexus of cancer therapy and the treatment of other serious ailments,” said Damian Green, M.D., the Ron and Nedra Kalish Family Endowed Chair in Stem Cell Transplantation and professor of medicine and chief of the Division of Transplantation and Cellular Therapy at Sylvester. “There are leaps that occur in cancer treatment and with cellular therapy. We are at one of those points where we’re seeing really dramatic benefits. Translating what we’ve learned to patients with autoimmune disease is a tremendous opportunity to help other patients also facing serious, life-threatening conditions.” 

The B Cell Connection

Although they are very different diseases, lymphoma and autoimmune disease have something important in common: B cells.

These immune cells turn malignant in many types of lymphoma. B cells are also the antibody-production factories of our bodies and, as such, they can make the antibodies that erroneously attack a patient’s own tissues in autoimmune disease. 

“There are leaps that occur in cancer treatment and with cellular therapy,” says Dr. Damian Green. “We are at one of those points where we’re seeing really dramatic benefits.”

Very recently, researchers have begun testing CAR T therapy on small groups of patients with chronic autoimmune diseases. The results are startling. Once eliminated by the cellular therapy, the patients’ B cells can come back healthy, with no sign of the self-directed antibodies that are the hallmark of autoimmune disease. 

Researchers are calling this an “immunological reset.” If this reset holds up beyond these initial trials, it would mean that a single infusion of the cellular therapy might cure autoimmune diseases. The B cells also seem to grow back much faster in autoimmune patients than they do in cancer patients. 

An Innovative Clinical Trial

The therapy tested in the trial underway at Sylvester and elsewhere uses CAR T cells that target a protein known as CD19, which is found on the surface of B cells. In CAR T therapy, researchers genetically engineer a patient’s own immune cells to recognize and kill diseased cells in the body. In the case of B-cell lymphomas, the therapy kills both healthy and malignant B cells. The healthy B cells eventually grow back, in many cases without any of the original cancer. 

The trial is enrolling patients with:

• Lupus

• Systemic sclerosis (or scleroderma), an autoimmune disease characterized by excessive scar formation and skin thickening

• Polymyositis, an autoimmune disease that causes muscle weakness. 

The Sylvester team just recently treated the first patient on this trial at the center and will soon treat another scleroderma patient. The first infusion of CAR T cells for an autoimmune patient reminded Lazaros Lekakis, M.D., professor in the Division of Transplantation and Cellular Therapy, of the day his team first treated a cancer patient with the cellular therapy. Both the scleroderma patient and the original lymphoma patient had some neurological side effects from the T cells. Researchers now know those effects to be common—and how to treat them.

“Ten years ago, we didn’t know what the heck we were looking at,” said Dr. Lekakis, a professor of clinical medicine at the Miller School who leads the Sylvester site of the clinical trial. “Now, we know what to do.”

With treatment, the scleroderma patient recovered quickly from the side effects and recently went home from the hospital. 

That story highlights why cancer experts like Dr. Lekakis and the highly specialized staff in the Division of Transplant and Cellular Therapy are leading the current charge in autoimmune disease, Dr. Green said. These physicians have years of experience treating patients with cellular therapy and monitoring their side effects. 

“The people who have the expertise to do this are right here at Sylvester,” Dr. Green said. “We know how to deal with the side effects and toxicities. We know how to manage these drugs, and that can be quite complicated.” 

Sylvester will also soon be a site for a second CAR T trial just for lupus patients. Dr. Lekakis and his colleagues are in discussions with neurologists at the Miller School about cellular therapy trials for neurological autoimmune diseases like multiple sclerosis. 

Trial Volunteers’ Impact Extends Beyond Cancer

The extension of cellular therapy to diseases beyond cancer points not only to the innovation of the researchers and physicians involved, but to the generosity of cancer patients themselves, Dr. Green said. CAR T therapy’s success is largely due to the cancer patients who volunteered for initial clinical trials, even if they knew the experimental treatment might not work for them. 

“When we tell patients, ‘We don’t know if this is going to work for you,’ the most frequent answer I hear is, ‘I understand, but it might help the next person,’” Dr. Green said. “Often, they’re saying the next person with my diagnosis, but it turns out it’s not just that. They’re actually helping a much broader population.”