$1 Million Bet on a Cure: Reprogramming the Immune System To Stop Type 1 Diabetes

A researcher is planning on investigating potential treatments aimed at the root causes of type 1 diabetes.

At the Medical University of South Carolina (MUSC), Leonardo Ferreira, Ph.D., is taking on type 1 diabetes (T1D) with support from a $1 million grant from Breakthrough T1D, the world’s leading organization focused on T1D research and advocacy. Ferreira, an assistant professor of Pharmacology and Immunology, and collaborators at partner institutions will investigate a new strategy aimed at treating and potentially curing the disease.

The researchers are combining stem cell biology, immunology, and transplantation science to rethink how the immune system and pancreas can coexist. Their central objective is to restore beta cell function and insulin production in people with T1D without relying on 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.”

Ferreira’s role draws on his experience reprogramming the immune system using chimeric antigen receptors, or CARs, designed to guide regulatory T-cells Tregs, to specific targets. Tregs help control the body’s immune response and are also important in autoimmune conditions such as T1D. In this context, they function like bodyguards, preventing immune activity from escalating to the point where it damages tissue and contributes to autoimmune disease. Ferreira is working alongside two well-known collaborators.

His co-principal investigator, Holger Russ, Ph.D., is an associate professor of Pharmacology and Therapeutics at the University of Florida and a leading specialist in stem cell research in T1D, which many see as a key direction for transplantation because it can provide an unlimited supply of islet cells for manufacturing and clinical use. The third partner is Michael Brehm, Ph.D., of the University of Massachusetts Medical School, a pioneer in humanized mouse models that are used to test and anticipate human immune and metabolic responses in human T1D.

Behind the Diagnosis: How T1D Works

T1D is an autoimmune disease in which the immune system mistakenly attacks the pancreas’s insulin-producing beta cells. When those cells are lost, the body can no longer control blood glucose levels, so people must depend on frequent blood sugar checks and insulin injections. According to the Centers for Disease Control and Prevention, about 1.5 million Americans live with the disease, which can cause complications including nerve damage, blindness, coma, and death.

The new Breakthrough T1D award builds on a 2021 Discovery Pilot grant from the South Carolina Clinical & Translational Research Institute (SCTR) that first made it possible for Ferreira and Russ to work together. That earlier support helped lay the groundwork for the current effort, which could change how T1D is understood and treated.

Agents in the new approach

Beta cells, which serve as the insulin factory of the pancreas, are depleted in people with T1D because their immune systems fail to recognize them as self and target them for destruction. Currently, patients with severe, difficult-to-manage T1D with exogenous insulin can receive a transplant of islet cells, which include beta cells.

While islet cell transplant therapy replenishes beta cells, it’s not without challenges. First, as they rely on human donors, it’s difficult to find enough beta cells for transplant. The team has tackled this issue by generating and producing its own stem-cell derived islet cells.

The second setback with this approach is that the transplanted beta cells, like any other organ/tissue/cells foreign to our self-body, are vulnerable to rejection by the immune system. This is where Ferreira’s expertise becomes critical. Because immune Tregs naturally help to restore and balance the immune system during and after immune activation, he engineers them with a CAR that can recognize a surface protein placed on the beta cells, acting like a GPS system that can be directed to reach a specific site. This allows the Tregs to act as targeted “bodyguards,” homing in on and protecting the beta cells, thereby creating a lock-and-key mechanism that does not occur in nature. When the receptor on the Treg – the “key” – fits into the protein on the beta cell – the “lock” – it sends a powerful message to the immune system to stand down. Working together, the beta cell and the Treg form a symbiotic partnership and protect the beta cell from immune attack after transplantation.

What’s the advantage of this approach? This combination cellular therapy – lab-produced beta cells that can make insulin along with their bodyguard Tregs to protect them from the immune response – would not require patients to take immunosuppressive drugs, which carry significant long-term risks, particularly in pediatric patients.

Moreover, the lab-grown cells could solve a longstanding logistical challenge in beta cell transplantation: the shortage of donor cells. Currently, a single transplant often requires beta cells from three or four donors, while most organ transplants need only a one-to-one match. The team’s engineered beta cells, by contrast, can be manufactured in the laboratory, frozen, and stored for extended periods without losing quality. This could ensure a reliable, scalable source of donor material for future treatments.

The ultimate goal is to generate a complete off-the-shelf therapy, melding the engineered Tregs with the novel beta cells to create a ready-to-use treatment that can be distributed widely 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.

Measuring success and looking ahead

Getting these therapies into clinics will take time. Ferreira and his team have a number of questions and obstacles to overcome before treatments can be offered to the public. For example, one of the key questions this study aims to answer is how long the treatment remains effective. In preclinical models using humanized mice, the effects last for up to a month, the longest time assessed. The new Breakthrough T1D grant will allow the team to investigate ways to extend this window, refine delivery methods, and evaluate whether combining multiple doses might yield more durable results.

By merging the disciplines of stem cell biology, gene editing, and immunoregulation, Ferreira’s team is creating not just a therapy but a model for how science can reprogram the body’s natural systems to heal itself. Their work may one day mean freedom from daily insulin injections and a future where type 1 diabetes is not just managed but cured.

If successful, this work could mark a turning point in regenerative and immune-based medicine.

“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.”

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