Their approach brings together stem cell science, immunology, and transplantation research. The central goal is straightforward but bold: restore insulin-producing beta cells in people with T1D without requiring immunosuppressive drugs.

“These awards support the most promising work that can significantly advance the path to cures for type 1 diabetes,” said Ferreira. “This is what Breakthrough T1D believes is the next wave in type 1 diabetes therapy.”

Engineering the Immune System to Protect Insulin Cells

Ferreira specializes in modifying the immune system using chimeric antigen receptors, or CARs. These engineered receptors help guide regulatory T cells, known as Tregs, to specific targets in the body. Tregs play an essential role in keeping immune responses under control and preventing excessive damage, including the autoimmune attack seen in T1D. In simple terms, they act like bodyguards, preventing the immune system from going too far and harming healthy tissue.

He is working alongside two prominent collaborators. Holger Russ, Ph.D., associate professor of Pharmacology and Therapeutics at the University of Florida, is a leader in stem cell research for T1D. Many scientists view this field as the future of transplantation because stem cells can provide a virtually unlimited supply of islet cells for research and clinical use. Michael Brehm, Ph.D., of the University of Massachusetts Medical School, completes the team. He is known for developing humanized mouse models that help researchers study human immune and metabolic responses in T1D.

What Happens in Type 1 Diabetes

Type 1 diabetes (T1D) is an autoimmune condition in which the immune system mistakenly attacks the pancreas’s insulin-producing beta cells. Without these cells, the body cannot properly regulate blood sugar levels. People with T1D must closely monitor their glucose and rely on insulin injections to survive. According to the Centers for Disease Control and Prevention, about 1.5 million Americans live with the disease. Over time, it can lead to serious complications, including nerve damage, blindness, coma, and even death.

The new Breakthrough T1D award builds on a 2021 Discovery Pilot grant from the South Carolina Clinical & Translational Research Institute (SCTR), which first brought Ferreira and Russ together. That early support laid the groundwork for this larger project, which could significantly reshape how T1D is treated.

A Two Part Cellular Therapy Strategy

In T1D, beta cells are destroyed because the immune system no longer recognizes them as part of the body. For patients with severe cases that are difficult to control with exogenous insulin, doctors can perform islet cell transplants, which include beta cells.

However, this option faces two major challenges. First, islet transplants depend on donor tissue, and there are not enough beta cells available. To address this shortage, the research team is producing its own stem cell derived islet cells in the laboratory.

The second problem is immune rejection. Transplanted beta cells, like any foreign tissue, can be attacked by the immune system. This is where Ferreira’s immune engineering expertise becomes essential. Tregs naturally help calm immune responses. Ferreira modifies these cells with a CAR that recognizes a specific surface protein placed on the beta cells. This works like a GPS signal, directing the Tregs precisely to the transplanted cells.

Once there, the engineered Tregs function as targeted “bodyguards,” protecting the beta cells from immune attack. The interaction works like a lock and key. When the receptor on the Treg fits the protein on the beta cell, it signals the immune system to stand down. Together, the beta cells and Tregs form a protective partnership that helps preserve insulin production after transplantation.

Avoiding Immunosuppressive Drugs

One major advantage of this combined cellular therapy is that it could eliminate the need for immunosuppressive drugs. These medications are commonly required after transplants but carry significant long term risks, especially for children.

Lab produced beta cells may also solve the long standing shortage of donor tissue. Currently, a single transplant can require beta cells from three or four donors, while most organ transplants involve a one to one match. In contrast, the team’s engineered beta cells can be manufactured in the lab, frozen, and stored without losing quality. This opens the door to a scalable and reliable supply for future treatments.

The ultimate aim is to create a complete off the shelf therapy that combines engineered Tregs with lab grown beta cells. Such a treatment could be widely distributed and administered through transplantation.

“We’re trying to develop a therapy that would work for all people with type 1 diabetes at every stage, even people who have had the disease for many years and have no beta cells left,” said Ferreira.

Testing Durability and Long Term Impact

Moving this therapy into clinical use will require time and further research. Several questions remain, including how long the protective effects last. In preclinical studies using humanized mice, the benefits have lasted up to one month, which is the longest period studied so far. The new funding will allow researchers to explore ways to extend this protection, improve delivery methods, and determine whether multiple doses could produce longer lasting results.

By combining stem cell biology, gene editing, and immune regulation, the team is developing more than a single therapy. They are building a framework for teaching the body to repair itself. If successful, this work could eventually free patients from daily insulin injections and shift type 1 diabetes care from lifelong management to a true cure.

The implications extend beyond diabetes. Success could represent a major advance in regenerative medicine and immune based therapies.

“I think this can change how medicine is done,” Ferreira said. “Instead of treating symptoms, we can actually replace the missing cells. By doing this work, we are likely to further understand how T1D starts, how it develops and how it can be treated.”