Philly biotech reports serious side effect in patient with lupus

A Philadelphia-based biotech company exploring new cell therapy applications said that a patient receiving CAR-T for an autoimmune disease experienced a serious adverse event.

The patient has a form of lupus that affects the kidney, and in late June, developed a neurological side effect that is a known risk of CAR-T from the therapy that the company is testing, called CABA-201. The company, Cabaletta Bio, said earlier this month that the condition “resolved rapidly following standard management.”

CAR-T therapy — short for chimeric antigen receptor T cell therapy — was pioneered at the University of Pennsylvania by cancer scientist Carl June and works by modifying the body’s own immune cells to attack disease-causing cells. Although initially heralded as a cure for blood cancers, researchers have suggested that it could have a lasting impact on other conditions such as heart disease and autoimmunity.

Still, some experts have raised concerns that CAR-T therapies could trigger secondary cancers, prompting the U.S. Food and Drug Administration to study patients who developed the blood cancer lymphoma after receiving CAR-T. In June, an FDA official offered some reassurance, saying any risk that CAR-T causes lymphoma is likely very small — far smaller than the risk of secondary cancer from some forms of chemotherapy.

So what does the setback for Cabaletta Bio’s lupus patient mean for CAR-T as a treatment for autoimmunity? For now, that remains unclear.

Cabaletta is continuing a clinical trial of its CABA-201 therapy at the same dose, but making other changes to protect patients, such as extra monitoring for fever and neurological symptoms.

As reported in Endpoints News, some analysts have cautioned that more adverse events in autoimmune patients treated with CAR-T may be on the horizon.

Autoimmunity occurs when a person’s immune cells begin to attack harmless cells in the body, creating autoimmune antibodies that target the person’s DNA, for example. What if CAR-T could be used to stop this process?

That’s something Penn researchers are now exploring in earnest, thanks in part to a recent $50 million gift to Penn’s Colton Center for Autoimmunity.

Cabaletta Bio — co-founded by Michael Milone, a Penn researcher who worked in June’s lab — is recruiting patients for clinical trials of CABA-201 in lupus, as well as the autoimmune diseases myositis, systemic sclerosis, and myasthenia gravis.