Readying Tregs for battle

Can therapies with defensive T cells fend off autoimmune diseases?

Within months, the FDA probably will approve the first drug to significantly slow the onset of type 1 diabetes among many at high risk of the disease. This success with the monoclonal antibody teplizumab will top three decades of struggles by immunologist Jeffrey Bluestone and partners.

This year, Bluestone launched Sonoma Biotherapeutics to take another giant leap against autoimmune disease—this one via reengineered immune cells.

“Cell therapy is really the next major medicine, but it’s hard and it’s not for the gentle,” Bluestone noted in an intriguing interview with John Carroll of Endpoints posted on September 30.

In Sonoma’s case, the defenders are a special force of T cells—T regulatory (Treg) cells, whose role in life is to prevent the main groups of T cells from shooting the wrong targets. Such rampages gone wrong drive type 1 diabetes, rheumatoid arthritis, lupus and other autoimmune diseases that together afflict more than 50 million in this country.

Rethinking and reconfiguring the Treg cells themselves might bring unique benefits, Bluestone believes.

“Our whole business model is that this is not a chronic treatment,” he told Carroll. “Your immune system is a living thing, so the drug you’re giving has to be a living thing. Otherwise you won’t control these diseases over the long run…. With Tregs, we can create something that might induce tolerance and require only a single therapy.”

Tregs already can act as multitalented natural pharmacies, churning out molecules for repair or regulation or many other cellular jobs, Bluestone pointed out. And since these regulatory cells evolved as brakes for the immune system, they also feature some built-in safety features.

As everywhere else in immunology, many open questions remain on Tregs, Bluestone and co-authors noted in a 2019 Nature Reviews article. Scientists don’t really understand how to distinguish Tregs in lymph nodes from Tregs in tissue, or in which location they’re active, or how to generate the most effective Treg therapeutic cells, or whether Treg cells will survive and keep functioning properly within patients, or….?

When and if these devils in the details are mastered, there’s a chance to build a unique treatment platform for many autoimmune diseases, he said. Maybe the method also will aid selected non-immune diseases such as brain degenerative illnesses.

Sonoma has gathered $70 million in early funding, during a year in which six other Treg companies also debuted. Bluestone applauds the competition: “It’s a great thing for the field.”

Treg cells in red (NIAID).