New Therapy Treats Autoimmune Disease Without Suppressing Immune System

Treatments for autoimmune diseases are hampered by a lack of understanding of specific immune cells at work in individual diseases. The first line of treatment is immune suppressants, like steroids or drugs often given to transplant recipients, which suppress all immune cells and leave the patient at increased risk of infection and cancers.

Now, promising new research from the Perelman School of Medicine at the University of Pennsylvania (UPenn) has found a way to target a specific subset of antibody-making cells in a rare autoimmune disease called pemphigus vulgaris (PV) without suppressing healthy immunity. The research, published recently in Science, could open the door to targeting other autoimmune diseases.

Autoimmune research is “stuck in the same dark ages as cancer therapy was decades ago, where they had no way of targeting cancer cells, so they just targeted all dividing cells,” study author Aimee S. Payne, an associate professor of dermatology at UPenn, tells mental_floss.

In PV, which causes blisters and sores in mucous membranes, a kind of immune cell called B cells attack a protein called desmoglein-3 (Dsg3), which typically helps skin cells adhere together. Until the advent of steroids and a drug therapy called Rituximab, the disease was usually fatal. “Now patients are no longer dying from the disease, which is good, but they have a lot of complications from the therapies,” Payne says.

Payne and her co-senior author Michael Milone adapted their autoimmune technique from an anti-cancer therapy called chimeric antigen receptor therapy, or CAR, in which T cells are engineered to kill cancerous cells in some leukemias and lymphomas. The cancer CAR therapy has been successful in human trials, though with some side effects. Payne’s team’s version is called CAART (chimeric autoantibody receptor therapy). The team designed an artificial CAR-type receptor in a mouse model that acts as “bait” to only those B cells producing the anti-Dsg3 antibodies, by attracting them to the engineered receptors and killing only them, and no other cells. They were able to successfully kill the Dsg3 cells without any symptoms of blistering or autoimmunity in the animals.

“The power of the CAR technology in general is that it has incredible specificity and potency at killing just what it’s designed to kill,” Payne says.

While CAR T cell therapy in cancer can cause a painful, almost sepsis-like syndrome called Cytokine Release Syndrome, Payne is confident that CAART will not be likely to cause this same condition in patients, because it is only targeting a very specific subset of B cells. “We’re not killing all of the B cells, only a small fraction of them. We think that in patients with active diseases, we’d be killing maybe at most one percent of your total B cells, the critical ones that are causing disease.”

Though Payne feels they have showed the “proof of concept” as well as cancer CAR therapy did before going to human trials, they will be attempting to cure dogs with the disease before moving on to human trials.

What they’ve learned from treating PV with this new autoimmune therapy will act “as a paradigm for all of the other auto-antibody mediated diseases,” Payne says. Not only is she hopeful about the future of treating autoimmune disease, but she sees this as another drop in the bucket of “personalized medicine” in which scientists will use genotyping to develop personalized therapies for a person’s disease “rather than treating everybody with a one-size-fits-all approach.”