Type 1 Diabetes Cell Therapy Tested in First-in-Human Study
A first-in-human study presented at the ISSCR 2026 Annual Meeting is testing whether immune-engineered, allogeneic insulin-producing cells can survive and function in people with type 1 diabetes without chronic immunosuppression.
The work addresses one of the main barriers to cell replacement therapy: immune rejection. Although replacing lost insulin-producing cells could restore biological insulin production, transplanted islet or stem cell-derived cells can be attacked by the recipient’s immune system, limiting broader use of the approach.
The study, presented by Sonja Schrepfer of Cedars-Sinai Medical Center, is evaluating whether hypoimmune engineering can protect transplanted allogeneic cells from immune attack while allowing them to persist and function.
“Type 1 diabetes is still treated primarily by replacing insulin, not by replacing the insulin-producing cells that were lost,” said Schrepfer in the ISSCR release. “Our goal is to develop a cell replacement approach that can survive and function without chronic immunosuppression.” Source
iPSC-Derived CAR T Tested for Systemic Sclerosis
Preliminary Phase 1 data presented at ISSCR 2026 suggest early signs of clinical improvement with Fate Therapeutics' off-the-shelf iPSC-derived CAR T-cell therapy for treatment-resistant systemic sclerosis.
The data come from the systemic sclerosis cohort of an ongoing Phase 1 basket trial evaluating FT819, an investigational allogeneic CAR T-cell therapy developed from induced pluripotent stem cells. Systemic sclerosis is a rare autoimmune disease that can affect the skin, lungs, gastrointestinal tract, heart, muscles, and joints. It has the highest mortality rate among rheumatic diseases, and no therapies are currently approved specifically to treat it.
FT819 is designed as an off-the-shelf alternative to conventional autologous CAR T-cell therapies, which require patient-specific manufacturing. Because the therapy is produced from an established iPSC cell bank, doses could potentially be made available more readily and distributed at scale.
The study enrolled patients with active, treatment-refractory systemic sclerosis who had experienced prior treatment failure. According to the ISSCR release, the therapy has so far shown a reassuring safety profile and has been administered in outpatient settings for patients with rheumatic diseases.
“Systemic sclerosis remains one of the most challenging autoimmune diseases to treat,” said Natalie Shiff of Fate Therapeutics in the release. “For many patients, simply stabilizing disease is considered a treatment success. That is why there is such an urgent need to develop new therapeutic approaches that have the potential to improve outcomes.” Source
Gene Therapy Restores Fragile X Traits in Mice
An AAV-based gene therapy designed to replace the missing protein behind fragile X syndrome restored several disease-relevant traits in a preclinical mouse study.
The study, led by Cincinnati Children’s, tested adeno-associated viral vectors carrying human FMR1, the gene silenced in fragile X syndrome. The condition is the most common inherited form of intellectual disability and a leading single-gene condition associated with autism. There is currently no cure, and treatment focuses on managing symptoms.
After testing several vector candidates, the team identified an approach that produced FMRP, the protein missing in fragile X syndrome, in key brain regions of Fmr1 knockout mice. Treatment reduced susceptibility to audiogenic seizures, improved sensory hyperactivity and repetitive digging behavior, and normalized elevated low-gamma EEG power, a brain activity marker also reported in human fragile X studies.
“These findings are important because they show that restoring FMRP can improve several fragile X-related traits in a model designed with clinical translation in mind,” said Christina Gross of Cincinnati Children’s in the release.
The study also explored delivery routes, promoters, and dosing strategies, with the authors arguing that EEG measures could help bridge preclinical studies and future human trials. Benefits were reported when the therapy was delivered at different age points, suggesting that some fragile X-related traits may remain modifiable after key stages of brain development. Source
CAR T Design Targets Mesothelin’s “Stump”
A mesothelin-targeting CAR T cell designed to avoid the effects of shed antigen has shown activity in preclinical models of ovarian and pancreatic cancer.
The CAR, known as CAR 422, targets a short juxtamembrane “stump” of mesothelin that remains on the tumor-cell surface after most of the protein is cleaved and shed. Conventional mesothelin-directed CAR T cells often target membrane-distal regions that can be lost through shedding, while soluble mesothelin in the tumor microenvironment may act as a decoy and limit tumor engagement.
Researchers at the University of Pennsylvania used a canine antibody phage display library to identify stump-binding single-chain variable fragments, then screened candidates in CAR T-cell formats. The lead candidate, CAR 422, showed tumor-control activity in pancreatic and ovarian cancer models, including an OVCAR8 model in which soluble shed mesothelin is expected to interfere with conventional mesothelin-targeted CAR T cells.
In mouse studies, CAR 422 controlled OVCAR8 tumors to baseline levels and produced long-term survival results similar to another stump-directed CAR, while a distal mesothelin-targeting CAR lost activity in the same model. The researchers also reported reduced on-target, off-tumor toxicity for CAR 422 in a human mesothelin knock-in mouse model compared with a conventional mesothelin CAR. Source
Allotera Raises $35 Million for Off-the-Shelf CAR T
Allotera Therapeutics, formerly Wugen, has closed a $35 million financing round to support pivotal-stage development of Soficabtagene Geleucel, an off-the-shelf CAR T-cell therapy for relapsed or refractory T-cell cancers.
The financing, made up of equity and venture debt, brings the company’s total Series C capital raised to $150 million. Proceeds will primarily support the ongoing global pivotal T-RRex trial of Sofi-cel in relapsed or refractory T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma, as well as platform development, operational scale-up, and team growth.
Sofi-cel is an allogeneic, healthy donor-derived, CD7-targeted CAR T-cell therapy. Allotera uses CRISPR/Cas9 gene editing to delete CD7 and TRAC, an approach intended to prevent CAR T-cell fratricide and reduce the risk of graft-versus-host disease. Source
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