We are making remarkable strides in understanding the levers of the human immune system: which signals tell it to attack, which tell it to stand down, and how we might selectively intervene in those pathways.

A small study in type 1 diabetes provides a fascinating new example.

Researchers at the University of Chicago transplanted pancreatic islet cells from deceased donors into 12 adults with long-standing type 1 diabetes. The islets contain the beta cells that produce insulin. All 12 patients subsequently became insulin-independent, with an average recent hemoglobin A1c of approximately 5.4%. No severe hypoglycemic episodes were reported following transplantation.

Islet transplantation itself is not new. But type 1 diabetes presents a particular immune challenge. The disease is autoimmune: the immune system has already attacked and destroyed the patient’s own insulin-producing beta cells. Transplanting healthy islets introduces a second problem. The recipient’s immune system can also recognize the donor cells as foreign and reject them.

Preventing that rejection has traditionally required powerful immunosuppressive drugs such as tacrolimus. These drugs can prevent the immune system from destroying the transplant, but at a cost: they can increase susceptibility to infection and other complications, and tacrolimus itself can damage the kidneys and even the insulin-producing beta cells the transplant is intended to restore.

The University of Chicago researchers instead used an experimental monoclonal antibody called tegoprubart, which targets CD40 ligand (CD40L), an important signaling pathway involved in activating an immune response.

In simple terms, instead of broadly suppressing the immune system, researchers are trying to interrupt the particular message that says: attack these transplanted cells.

The results were presented in June at the American Diabetes Association’s 2026 Scientific Sessions. The study is tiny, and the longest follow-up reported so far is 22 months. But 12 out of 12 patients becoming insulin-independent certainly warrants attention.

There is an important caveat. These patients have not simply traded diabetes for a medication-free life. Tegoprubart is currently given by intravenous infusion every three weeks, along with other immunosuppressive therapy, to protect the transplanted cells. The larger goal is eventually to achieve immune tolerance that would allow patients to be weaned from immunosuppression altogether. Researchers aren’t there yet.

Pulling the Immune System’s Levers

Monoclonal antibodies are increasingly being used to manipulate particular parts of the immune response.

In cancer, drugs such as pembrolizumab block PD-1, one of the mechanisms that can restrain T cells. Some cancers exploit this pathway to evade immune attack. Block the signal, and in some patients the immune system can attack the cancer more effectively.

The principle behind tegoprubart is almost the reverse. Researchers aren’t trying to unleash an immune attack. They are trying to prevent one.

Monoclonal antibodies also became familiar during the COVID-19 pandemic. Treatments such as casirivimab and imdevimab were designed to bind directly to the SARS-CoV-2 spike protein, blocking the virus from attaching to and entering human cells. Unlike a vaccine, which stimulates the body to produce its own antibodies, these treatments supplied laboratory-made antibodies directly. As the virus evolved, however, variants emerged that could evade many of these antibodies, and the treatments lost their effectiveness. It is another reminder of just how dynamic the immune system and its targets can be.

We are becoming increasingly sophisticated at identifying these different levers, but there is a danger in taking the analogy too far.

We’re learning what some of the levers do. Pull this one and the immune system attacks; pull another and it stands down. But we’re still operating a machine we don’t completely understand, and pulling one lever can have consequences elsewhere in the system.

The immune system does not operate in isolation. It is intertwined with the gut microbiome, the lymphatic system, metabolism, inflammatory signaling and countless other processes that vary from one individual to another. We understand considerably more about these relationships than we did even a decade ago, but nobody has a complete wiring diagram.

That is what makes this research both exciting and worth approaching with some humility.

For people with type 1 diabetes, the immediate significance is clear. If transplanted insulin-producing cells can be protected while reducing the toxicity associated with conventional immunosuppression, cell replacement becomes considerably more practical. Combine that with ongoing advances in producing pancreatic beta cells from stem cells, and the implications become even greater.

Twelve patients do not establish a new standard of treatment. Tegoprubart remains experimental, and we need longer follow-up.

But researchers appear to have identified another important lever, and this time, pulling it seems to be telling the immune system something very useful: leave these cells alone!

Sources and Further Reading

Breakthrough T1D — Tegoprubart Islet Transplant Results
12 patients achieve insulin independence.
https://www.breakthrought1d.org/news-and-updates/tegoprubart-islet-transplant-all-participants-off-external-insulin/

University of Chicago Medicine — Tegoprubart Trial
Clinical trial protocol and treatment details.
https://www.uchicagomedicine.org/find-a-clinical-trial/clinical-trial/irb231367

New England Journal of Medicine — Stem Cell-Derived Islets
Stem-cell islets restore insulin production.
https://www.nejm.org/doi/10.1056/NEJMoa2506549

PubMed — Pembrolizumab and PD-1
Checkpoint blockade enables antitumor immunity.
https://pubmed.ncbi.nlm.nih.gov/40635600/

FDA — COVID-19 Monoclonal Antibodies
Antibodies targeting SARS-CoV-2 spike protein.
https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-monoclonal-antibodies-treatment-covid-19

PubMed — Gut Microbiota and Immunity
Microbiome interactions shape immune responses.
https://pubmed.ncbi.nlm.nih.gov/38722348/

PubMed — Lymphatic System and Immunity
Lymphatics actively regulate immune function.
https://pubmed.ncbi.nlm.nih.gov/33923289/