Off-the-shelf cell therapy shows early promise as scleroderma treatment
Gains seen for first 4 people with hard-to-treat disease in large clinical trial
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An investigational off-the-shelf, or readily available, CAR T-cell therapy has shown early signs of effectiveness — with clinical improvements and no serious safety concerns — in the first four people with systemic sclerosis (SSc) treated in an ongoing clinical trial in the U.S. and Europe.
That’s according to preliminary findings from the large Phase 1 study (NCT06308978), which is evaluating the cell therapy FT819 in adults and children with moderate to severe autoimmune diseases, including SSc, who continue to have symptoms despite receiving at least two previous therapies. The trial, which is still enrolling, is recruiting people ages 12 to 70 at 21 sites in the U.S., the U.K., Sweden, and France.
To involve a broader range of participants, the researchers expanded the maximum disease duration allowed for enrollment. Eligible participants now range from newly diagnosed patients to those who have been living with their disease for as long as 15 years.
The study’s findings to date will be presented at this year’s International Society for Stem Cell Research (ISSCR) annual meeting, Fate Therapeutics, the therapy’s developer, announced in a company press release. The ISSCR meeting will be held July 8-11 in Montreal.
In SSc, also known as scleroderma, the immune system mistakenly attacks the body’s own healthy tissues. This triggers inflammation and the formation of scar-like tissue, causing the skin to become thick and tight. The disease can also affect internal organs, including the lungs, heart, and kidneys, as well as the digestive tract. While available treatments can help manage symptoms, none can stop or reverse the disease.
In recent years, CAR T-cell therapies have emerged as a promising approach for several autoimmune diseases. Traditionally, the treatment involves collecting a patient’s own T-cells — immune cells that normally help defend the body against infections — and genetically engineering them in the lab to produce a man-made receptor, called a chimeric antigen receptor (CAR).
This receptor acts like a molecular GPS, allowing the engineered T-cells to recognize a protein on the surface of B-cells, which are immune cells that produce the harmful antibodies that drive many autoimmune diseases, including SSc. Once infused back, these cells seek out and destroy harmful B-cells.
Meaningful improvements in skin thickening seen for all 4 patients
FT819 is designed to target the CD19 protein on B-cells. Unlike conventional CAR T-cell therapies, which are individually manufactured from each patient’s own immune cells, FT819 is produced from induced pluripotent stem cells (iPSCs) derived from healthy donors. iPSCs are adult cells that have been reprogrammed into a stem cell-like state, allowing them to generate large numbers of different cell types.
This so-called off-the-shelf approach allows therapy to be manufactured in advance, potentially making treatment readily available while reducing production time and cost.
The ongoing Phase 1 trial is evaluating FT819’s safety, its pharmacokinetics — how it moves through the body — and its early effectiveness across several conditions. Among the participants are people with systemic lupus erythematosus, the most common form of lupus, including individuals with or without kidney damage, as well as people with ANCA-associated vasculitis and idiopathic inflammatory myositis, for whom the condition has no known cause.
An initial dose-escalation period is being followed by an expansion stage to further evaluate the therapy’s safety and efficacy.
At the time of the analysis, four people with scleroderma had received FT819 and completed at least three months of follow-up. Three received the therapy after less-intensive conditioning chemotherapy, which helps deplete T-cells and make room for the modified ones, using either cyclophosphamide or bendamustine alone. The fourth patient received FT819 without any conditioning chemotherapy.
Three months after treatment, all four achieved a score of at least 25 on the Revised Composite Response Index in Systemic Sclerosis (rCRISS). An rCRISS score of 25 or higher is considered evidence of an overall clinical improvement, taking into account changes in skin thickening, lung function, functional ability, and both physician and patient assessments of disease severity.
Participants also showed meaningful mean improvements in their modified Rodnan Skin Score (mRSS), the standard measure of skin thickening.
CAR T-cell therapy so far safe, well tolerated
FT819 also appeared to be generally well tolerated. None of the participants experienced cytokine release syndrome, a potentially life-threatening overreaction of the immune system, or immune effector cell-associated neurotoxicity syndrome (ICANS), a potentially serious complication affecting the brain.
There were also no cases of graft-versus-host disease, in which donor immune cells attack the recipient’s healthy tissues, no cases of hypogammaglobulinemia, a condition marked by abnormally low antibody levels that can increase the risk of infections, and no treatment-related deaths.
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