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Donor islet transplantation has long offered an intriguing possibility for people with severe type 1 diabetes: restore the body’s ability to make insulin instead of only replacing insulin from the outside. However, there has always been a major tradeoff. Patients need powerful immunosuppressive drugs to keep transplanted cells alive, and those medicines can cause serious long-term problems. Now, early research into a tegoprubart islet transplant strategy is exploring whether donor islets can be protected with more targeted immunosuppression and less reliance on traditional drugs such as tacrolimus. The latest results are encouraging, although important questions remain.
Table of Contents
- Why islet transplantation needs safer immunosuppression
- How tegoprubart may support islet transplantation
- What the early clinical results show
- What this research could mean for type 1 diabetes
- Conclusion
- Frequently asked questions
Why Islet Transplantation Needs Safer Immunosuppression
Pancreatic islets contain beta cells, which produce insulin in response to changing blood glucose levels. In type 1 diabetes, the immune system destroys these insulin-producing cells. Therefore, replacing functional islets can potentially restore the body’s own insulin production.
During an allogeneic islet transplant, islets are collected from a deceased donor and infused into the recipient, typically through the portal vein into the liver. Once established, the transplanted cells can begin sensing glucose and releasing insulin. For selected patients, this approach can greatly improve glucose control and may eliminate the need for external insulin for a period of time.
However, the recipient’s immune system recognizes donor cells as foreign. As a result, patients require ongoing immunosuppression to prevent rejection.
Calcineurin inhibitors such as tacrolimus have traditionally played an important role in transplant medicine. Yet tacrolimus can cause kidney, neurological, metabolic, and other toxicities. Importantly for islet transplantation, calcineurin inhibitors may also harm the insulin-producing cells clinicians are trying to preserve.
Consequently, researchers have been searching for an immune strategy that protects transplanted islets without exposing them to the same level of calcineurin inhibitor toxicity. An islet transplant regimen using tegoprubart could offer one potential answer.
How Tegoprubart May Support Islet Transplantation
Tegoprubart, also known as AT-1501, is an investigational monoclonal antibody that targets CD40 ligand, or CD40L. The CD40-CD40L pathway helps immune cells communicate and plays an important role in the immune response that can lead to transplant rejection.
By blocking this pathway, tegoprubart aims to reduce the immune response against donor tissue. More importantly, researchers are studying whether this targeted approach can replace tacrolimus as the core anti-rejection therapy after an islet transplant.
An ongoing clinical study listed on ClinicalTrials.gov is evaluating a calcineurin inhibitor-free regimen in adults with type 1 diabetes and problematic hypoglycemia.
Still, “calcineurin inhibitor-free” does not mean “immunosuppression-free.” Participants receive tegoprubart alongside other immunosuppressive medicines. Therefore, the goal is not yet to eliminate immune suppression altogether. Instead, investigators are testing whether they can remove tacrolimus and its associated burden while maintaining effective graft protection.
That distinction matters when discussing the potential impact of the study. Tegoprubart is investigational, and neither the drug nor this transplant regimen represents a broadly approved cure for type 1 diabetes.
Early Islet Transplant Results With Tegoprubart Draw Attention
The latest findings have created considerable interest because the initial clinical outcomes are striking. According to results presented at the American Diabetes Association’s 86th Scientific Sessions in June 2026, all 12 participants in the initial reported cohort achieved insulin independence after receiving donor islet transplantation with tegoprubart-based immunosuppression.
In other words, the participants were producing endogenous insulin and no longer required chronic external insulin therapy at the time of the update. Moreover, every participant’s most recent HbA1c was below 6.5%. The mean was approximately 5.4%, compared with a mean baseline HbA1c of about 8.0%, according to results reported by Eledon Pharmaceuticals.
The hypoglycemia findings are also notable. Before transplantation, all enrolled participants had histories of recurrent severe hypoglycemic events. Following transplantation, researchers reported no severe hypoglycemic episodes in the cohort.
Additionally, investigators reported no transplant rejection episodes and no newly developed donor-specific HLA antibodies. At the June update, graft function remained stable over a median follow-up of eight months, while the longest follow-up had reached 22 months.
Researchers also reported no evidence of the nephrotoxicity, hypertension, or neurotoxicity commonly associated with tacrolimus-based immunosuppression in the cohort. These findings build on earlier results from the first six participants, who also achieved insulin independence after one or two islet transplants.
However, these remain early results from a small, non-randomized study. ClinicalTrials.gov lists the trial as ongoing, with an estimated enrollment of 70 participants and study completion projected for 2029. Therefore, longer follow-up and larger studies will be essential to determine durability and safety.
What Could This Mean for Type 1 Diabetes Treatment?
For decades, beta-cell replacement has faced two linked challenges. Scientists must provide enough functioning insulin-producing cells, and they must prevent the immune system from destroying those cells.
A successful tegoprubart-based immunosuppression strategy for islet transplantation could potentially improve the second half of that equation. If targeted CD40L blockade can protect donor islets while reducing reliance on calcineurin inhibitors, transplanted cells may face a more favorable environment after infusion.
That possibility could become increasingly important as cell-replacement technologies advance. Researchers are exploring donor islets, stem-cell-derived islets, encapsulation systems, and other methods designed to restore insulin production. However, any approach involving immune-visible replacement cells must address rejection and recurrent autoimmunity.
There are also practical limits to consider. Donor islets are scarce, transplantation requires specialized medical expertise, and recipients still face risks from immunosuppression. Therefore, even highly successful results would not automatically make islet transplantation appropriate for everyone with type 1 diabetes.
In addition, insulin independence should not be confused with a permanent cure. Researchers need longer-term evidence showing how well the transplanted cells survive and whether patients remain free from insulin over several years.
Still, the early results provide an important proof of concept. They suggest that researchers may be able to rethink how immune protection is delivered rather than simply accepting the toxicities of older transplant regimens.
A second clinical study is also examining tegoprubart-based, calcineurin inhibitor-free immunosuppression with pancreatic islet transplantation in adults who have type 1 diabetes and chronic kidney disease. As this research progresses, clinicians should gain a clearer picture of where this strategy may fit within the rapidly changing beta-cell replacement landscape.
Patients interested in emerging diabetes treatments should discuss clinical trials and treatment options with their diabetes care team. They can also search for recruiting studies through ClinicalTrials.gov.
Conclusion
The use of tegoprubart in islet transplantation addresses one of the central problems that has held donor islet transplantation back: protecting insulin-producing cells without relying on a calcineurin inhibitor such as tacrolimus.
Early results are promising. All 12 participants in the initial reported cohort achieved insulin independence, mean HbA1c reached approximately 5.4%, and no severe hypoglycemic episodes were reported after transplantation. Researchers also reported no rejection episodes and no evidence of several toxicities associated with tacrolimus during the available follow-up.
Nevertheless, this is still early-stage research. The study is small, open-label, non-randomized, and ongoing. Tegoprubart also does not eliminate the need for immunosuppression. Larger studies and longer follow-up will determine whether the benefits remain durable and whether the safety profile continues to hold.
For people living with difficult-to-manage type 1 diabetes, however, the research points toward an important possibility: restoring insulin production while making the immune protection needed to preserve those cells more targeted and potentially less toxic.
Frequently Asked Questions
How is tegoprubart being used with islet transplantation?
Tegoprubart is being studied as part of an experimental immunosuppressive regimen for people receiving donor pancreatic islets. Researchers are evaluating whether its targeted effects on the CD40-CD40L pathway can help prevent rejection without relying on calcineurin inhibitors such as tacrolimus.
Is tegoprubart approved for type 1 diabetes?
No. Tegoprubart is investigational, and the current islet transplant studies are clinical research. Its safety and effectiveness for this use have not been established through regulatory approval.
Did everyone in the initial trial stop taking insulin?
According to the June 2026 investigator-initiated trial update, all 12 participants in the reported cohort achieved insulin independence. However, follow-up remains limited, and the ongoing trial is expected to enroll more participants.
Does tegoprubart eliminate immunosuppressive drugs?
No. The experimental strategy is designed to eliminate calcineurin inhibitors such as tacrolimus from the regimen, but participants still receive other immunosuppressive therapies. Therefore, this approach should not be described as immunosuppression-free.
Could this become a cure for type 1 diabetes?
It is too early to call the approach a cure. The findings show promising restoration of insulin production in a small cohort, but researchers still need larger trials and years of follow-up to understand durability, long-term safety, and which patients could benefit most.
This content is not medical advice. For any health issues, always consult a healthcare professional. In an emergency, call 911 or your local emergency services.