CAR-T Therapy Expands Beyond Cancer: Ireland Milestone, New Trials and Genetic Insights

More than 150 patients have received CAR-T therapy in Ireland since the treatment was introduced five years ago, a milestone for a therapy that can provide an effective cure for around 40-50 percent of patients with chemotherapy-resistant lymphoma. St James’s Hospital in Dublin treated its first patient with CAR-T therapy in December 2021, and has since treated patients from across the country. CAR-T therapy enlists the patient’s own immune system to fight cancer: T-lymphocytes are removed from the blood, genetically engineered to express a chimeric antigen receptor (CAR) which recognises the tumour cell surface antigen, grown in the laboratory, and infused back into the patient, where they bind to the antigen on the tumour cells and kill them.

In Ireland, CAR-T treatment is reserved for certain blood cancer patients who have responded poorly to chemotherapy, or where their disease has relapsed within a short timeframe, according to a consultant haematologist at St James’s. The majority of Irish patients who have received the treatment have had high-grade lymphoma, with a smaller number of patients with acute lymphoblastic leukaemia also receiving the therapy. The number of patients treated has increased year-on-year, with 45 people treated last year and that number expected to be even higher in 2026. It is expected that the opening of a CAR-T therapy treatment facility in University Hospital Galway will provide access to the treatment for even more patients in the future.

CAR-T therapy is also being explored for autoimmune diseases. A 37-year-old woman with severe lupus who received a one-off CAR-T treatment at Addenbrooke’s Hospital in Cambridge in summer 2025 as part of a Phase I trial said one year later the therapy had transformed her life. 'This is the first time since I was a teenager that I've really felt healthy,' she said, calling the treatment 'the best decision I ever made.' Cambridge University Hospitals has now become the first in the world to begin recruiting patients into a larger Phase II trial of the therapy, developed by UK biotech company Autolus. CAR-T therapy works by collecting a patient’s immune cells, modifying them in a laboratory and returning them to the bloodstream, where they target the harmful immune cells responsible for the disease. Around one in every 1,000 people is affected by systemic lupus erythematosus, a chronic autoimmune disease that can damage the joints, skin, kidneys, heart and other organs.

In multiple sclerosis, CAR T aims to reset the immune system by depleting B cells which are believed to be driving the autoimmune attack causing the disease. A 40-year-old patient from Rotherham was the first patient in Sheffield and the seventh in a global trial to receive CAR T-cell therapy as a potential treatment for MS. The trial, known as AUTOMS-1 or BOBCAT, is assessing if CAR T-cell therapy could be a potential treatment for MS and is open to patients aged 18 to 60 years diagnosed with progressive MS who are not responding well to existing medication and where disability is worsening. Researchers will recruit up to 18 patients globally, with the first phase focused on testing the safety of the therapy.

While no CAR-T treatments have been authorized by regulators to treat autoimmune conditions yet, Kyverna Therapeutics’ miv-cel is poised to gain approval by the end of this year. Miv-cel targets the antigen CD19 and is designed to reduce cytokine release and eliminate harmful B cells. Data from a phase 2 study showed a single dose improved mobility in patients with stiff person syndrome, reversed disability scores, and removed the need for immunotherapies. The company began a rolling Biologics License Application submission to the U.S. Food and Drug Administration in May and is expected to complete the filing by the end of the year. Phase 2 studies of the therapy are also being conducted in myasthenia gravis. Cabaletta Bio is developing rese-cel, a fully human CD19 CAR-T therapy, in phase 1/2 trials for systemic lupus erythematosus. CAR-T therapies have been on the market to treat cancer since Kymriah was first approved in 2017.

New research has shown that patients’ inherited genetic makeup can influence whether they benefit from CAR T-cell therapy or experience toxicity. Investigators at Massachusetts General Hospital, Dana-Farber Cancer Institute, and the Broad Institute of MIT and Harvard sequenced the entire genomes of more than 200 patients with aggressive lymphoma from two major clinical trials of CAR T-cell therapy. They found that in one trial, patients with T cells containing variants that silenced the gene STXBP2 tended to experience treatment-related toxicity. Variants in a gene called ADAMTSL3 correlated with protection from toxicity, and variants in PTPN22 were strongly associated with enhanced CAR T-cell expansion, a key determinant of the therapy’s efficacy. The results suggest that variants in these genes can shape the safety and therapeutic activity of CAR T-cell therapies and may be useful for screening donors for future allogeneic CAR T-cell therapies.

Despite progress, challenges remain in the field, including the cost and technical complexity of phenotyping, profiling, and purifying immune cells, as well as variable patient responses. Each CAR T-cell product is uniquely manufactured from the cells of a patient or donor, and efforts are underway to better understand the mechanistic basis of treatment outcomes and to improve construct longevity, selectivity, manufacturing, and delivery.