{
  "abstract": "Introduction Systemic sclerosis (SSc) is associated with a high morbidity and mortality (1, 2). Immunosuppressive and cellular therapies such as autologous stem cell transplantation (HSCT) are used (3). Chimeric antigen receptor (CAR) T cell therapy is a promising alternative option (4-8). Here we report an update on our experiences with CD19-targeting CAR T cells in a cohort of 7 patients with SSc.Material and Methods CAR T cells were produced in our academic Good Manufacturing Practice laboratory with a human anti-CD19 lentiviral construct and amplification in a CliniMACS Prodigy (both produced by Miltenyi Biotech; Gladbach, Germany) as recently published (8). Subsequent to lymphodepletion CAR T cells were reinfused.Response to treatment was defined as either improvement of >25% in skin thickness meassured by modified rodnan skin score (mRSS) or >10% improvement in lung function tests (PFT) diffusing capacity for carbon monoxide (DLCO) or forced vital capacity (FVC, in % predicted) or weight gain in patients with gastrointestinal involvement within the first 12 months.Results From July 2023 to August 2025, 7 patients (6 female, one male) were treated with Anti-CD19 CAR T cells. Two patients had a relapse after HSCT after 8 and 24 months. In all patients CAR T cells expanded and B-cells were depleted.After a median follow-up of 18 months (range 3 – 29) we observed response to treatment in 4 patients. In 2 patient no response (shortest follow-up) but stable disease was observed and 1 patient has relaspsed after response at month 24. As published recently, 1 patient died on day 74 after CAR T cell therapy due to herpes infection and haemophagocytosis. No patient had signs of moderate/ severe CRS or Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS).In 5 patients mRSS significantly improved (p=0.09). Four patients displayed an improvement in DLCO and FVC. Two patients exhibited no change in PFT results, while 1 patient demonstrated a decline in DLCO and FVC after initial response. An increase in BMI was observed in five patients.Conclusions This is the second large cohort of anti-CD19 CAR T cell treated patients with SSc. In 5/7 patients a response was observed over the 18 months follow up. Both patients with relapse after HSCT showed response to treatment. But there are also 2 patients that did not response or relapsed despite effective B-cell depletion and 1 patient died. Data from prospective controlled trials are needed to further evaluate the value of this treatment option.",
  "authors": [
    {
      "affiliations": [
        "University Hospital Tübingen, Tübingen, Germany"
      ],
      "name": "Luisa Schneider"
    },
    {
      "affiliations": [
        "University Hospital Tübingen, Tübingen, Germany"
      ],
      "name": "Ann-Christin Pecher"
    },
    {
      "affiliations": [
        "University Hospital Tübingen, Tübingen, Germany"
      ],
      "name": "Wolfgang Bethge"
    },
    {
      "affiliations": [
        "University Hospital Tübingen, Tübingen, Germany"
      ],
      "name": "Claudia Lengerke"
    },
    {
      "affiliations": [
        "University Hospital Tübingen, Tübingen, Germany"
      ],
      "name": "Jörg Henes"
    }
  ],
  "title": "P.248 Anti-CD19 CAR T cell therapy in systemic sclerosis - update on seven patients from tuebingen",
  "uid": "2c368f1e-eb8b-5a6e-957f-d9777a7eda86"
}