Today at ISSCR 2026, new preliminary clinical data was presented evaluating an induced pluripotent stem cell (iPSC)-derived CAR T-cell therapy for patients with treatment-resistant systemic sclerosis, a rare autoimmune disease with high mortality.
The presentation highlights early findings from the systemic sclerosis cohort of an ongoing Phase 1 basket trial evaluating FT819, an investigational off-the-shelf iPSC-derived CAR T-cell therapy, in autoimmune diseases.
Systemic sclerosis can affect multiple organs – including the skin, lungs, gastrointestinal tract, heart, muscles, and joints – and has the highest mortality rate among rheumatic diseases. Patients typically experience worsening disease over time, and current treatment approaches are largely focused on slowing progression rather than improving symptoms. No therapies are currently approved specifically to treat systemic sclerosis.
"Systemic sclerosis remains one of the most challenging autoimmune diseases to treat," said Natalie Shiff, M.D., Fate Therapeutics Inc., USA. "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."
The study is enrolling patients with active, treatment-refractory systemic sclerosis who experienced prior treatment failure. Unlike some previous studies, eligibility does not include an upper limit on disease duration, allowing investigators to evaluate the therapy across a broader spectrum of patients and supporting the goal of making treatment accessible to a wider patient population.
FT819 is designed as an off-the-shelf iPSC-derived CAR T-cell therapy, offering a different approach from conventional autologous CAR T-cell therapies that require individualized manufacturing. Because FT819 is produced from an established iPSC cell bank, doses can be readily available and have the potential to support scalable distribution. To date, the therapy has demonstrated a reassuring safety profile and has been successfully administered in outpatient settings for patients with rheumatic diseases. The development of FT819 was in part made possible by funding from the California Institute for Regenerative Medicine (CIRM), a state agency in California that supports research in regenerative medicine, stem cell therapy, gene therapy, and clinical trials (Grant number: CLIN2-16303).
"Improving access is an important part of advancing cell therapy for autoimmune disease," said Dr. Shiff. "An off-the-shelf approach has the potential to reduce many of the manufacturing and logistical challenges associated with personalized cell therapies while expanding access to patients who might otherwise face barriers to receiving these treatments."
Although the study remains in its early stages, preliminary observations have identified signals of clinical improvement. If confirmed in larger studies with longer follow-up, the findings could represent an important advance for patients living with systemic sclerosis by improving quality of life, reducing disease burden, and potentially altering the long-term course of disease.
"While these findings require additional study, the early signals are encouraging for a patient population with significant unmet medical needs," said Dr. Shiff. "Our next steps are to continue evaluating the safety, efficacy, and durability of FT819 in systemic sclerosis and other rheumatic diseases, while identifying which patients are most likely to benefit."
Beyond systemic sclerosis, investigators believe the platform has broader applications across autoimmune diseases. FT819 is also being evaluated in lupus as part of an ongoing basket trial, with a planned Phase 2 potentially registrational trial in lupus nephritis.
Dr. Shiff noted that presenting the findings at ISSCR 2026 is especially meaningful because FT819 is derived from induced pluripotent stem cells, reflecting decades of stem cell research that have advanced understanding of pluripotency, differentiation, and cell-based therapies.
To learn more about ISSCR 2026 visit www.isscr2026.org
