{
  "abstract": "Introduction Treatment goals for systemic sclerosis (SSc) include controlling disease activity, limiting progression of organ damage and decreasing morbidity and mortality. Therapies providing clinical responses and durability are lacking. Rese-cel is a fully human, autologous 4-1BB CD19-CAR T cell therapy designed to deeply and transiently deplete CD19 positive cells following a single weight-based infusion, enabling an ‘immune system reset’ with the potential for durable response without the need for chronic immunomodulatory (IM) therapy. RESET-SSc ( NCT06328777) is an ongoing Phase 1/2 trial evaluating rese-cel in adult SSc patients.Material and Methods Eligible patients were 18 to 75 years with SSc and severe skin or organ involvement. 1x10^6 CAR T cells/kg was administered following preconditioning with fludarabine and cyclophosphamide. All non-glucocorticoid (GC) IM agents were stopped by Day -5. Adverse events, modified Rodnan skin score (mRSS), pulmonary function test (PFTs), nailfold capillaroscopy (NFC) and IM medications were evaluated. CAR T and B cells were profiled in peripheral blood by digital PCR and flow cytometry. Serum cytokines were measured using the mesoscale discovery platform. Inguinal lymph node biopsies were taken before and 21-days after rese-cel in SSc-Skin-1 and labeled for B cells and T cells.Results As of 6 May 2025, 2 patients were infused with rese-cel ( table 1). Updated data will be presented at the Congress.SSc-Skin-1 had grade 2 cytokine release syndrome (CRS) but no immune effector cell-associated neurotoxicity syndrome (ICANS). SSc-Skin-2 experienced grade 3 ICANS based on a brief period of confusion without seizures, motor findings, or cerebral edema, which resolved in <2 days with GC.Both patients showed improvement in mRSS off all IM therapy: 42 at baseline to 34 at 6 months in SSc-Skin-1 and 38 to 31 at 1 month in SSc-Skin-2. PFTs and NFC in SSc-Skin-1, also improved at 6 months.By Day 15, both patients exhibited peak expansion of rese-cel, peripheral B cell depletion and elevations in serum BAFF levels. SSc-Skin-1 exhibited B cell depletion in lymphoid tissue (figure 1) at Day 21. SSc-Skin-1 B cells began reconstituting by Week 8 post infusion with a transitional naïve phenotype (CD19+CD20+CD38++CD24++) and switched to predominantly mature naïve by Month 6.Conclusions Data in SSc patients infused with rese-cel show early IM-free clinical response and acceptable safety profile following rese-cel expansion and complete peripheral and lymph node B cell depletion. These data suggest the potential for rese-cel to reset the immune system in SSc, allowing patients to achieve meaningful clinical responses off IM therapies.Abstract P.257 Figure 1B cells depleted from inguinal LN tissue at Day 21 post-infusion in SSc-Skin-1Abstract P.257 Table 1Baseline characteristics",
  "authors": [
    {
      "affiliations": [
        "University of Michigan, Ann Arbor, USA"
      ],
      "name": "Dinesh Khanna"
    },
    {
      "affiliations": [
        "University of Michigan, Ann Arbor, USA"
      ],
      "name": "Monalisa Ghosh"
    },
    {
      "affiliations": [
        "Duke University, Durham, USA"
      ],
      "name": "Ankoor Shah"
    },
    {
      "affiliations": [
        "Duke University, Durham, USA"
      ],
      "name": "Sonali Bracken"
    },
    {
      "affiliations": [
        "Northwestern University, Evanston, USA"
      ],
      "name": "George Georges"
    },
    {
      "affiliations": [
        "Northwestern University, Evanston, USA"
      ],
      "name": "Carrie Richardson"
    },
    {
      "affiliations": [
        "University of Rochester, Rochester, USA"
      ],
      "name": "Benjamin Korman"
    },
    {
      "affiliations": [
        "Columbia University, New York City, USA"
      ],
      "name": "Elena Bernstein"
    },
    {
      "affiliations": [
        "University of Michigan, Ann Arbor, USA"
      ],
      "name": "PS Tsou"
    },
    {
      "affiliations": [
        "University of Michigan, Ann Arbor, USA"
      ],
      "name": "Charles Ross"
    },
    {
      "affiliations": [
        "University of Michigan, Ann Arbor, USA"
      ],
      "name": "Carleigh Zahn"
    },
    {
      "affiliations": [
        "Cabaletta Bio, Philadelphia, USA"
      ],
      "name": "Courtney Little"
    },
    {
      "affiliations": [
        "Cabaletta Bio, Philadelphia, USA"
      ],
      "name": "Mikaela Raymond"
    },
    {
      "affiliations": [
        "Cabaletta Bio, Philadelphia, USA"
      ],
      "name": "Adreeja GuhaRay"
    },
    {
      "affiliations": [
        "Cabaletta Bio, Philadelphia, USA"
      ],
      "name": "Jenell Volkov"
    },
    {
      "affiliations": [
        "Cabaletta Bio, Philadelphia, USA"
      ],
      "name": "Daniel Nunez"
    },
    {
      "affiliations": [
        "Cabaletta Bio, Philadelphia, USA"
      ],
      "name": "Thomas Furmanak"
    },
    {
      "affiliations": [
        "Cabaletta Bio, Philadelphia, USA"
      ],
      "name": "Jason Stadanlick"
    },
    {
      "affiliations": [
        "Cabaletta Bio, Philadelphia, USA"
      ],
      "name": "Larissa Ishikawa"
    },
    {
      "affiliations": [
        "Cabaletta Bio, Philadelphia, USA"
      ],
      "name": "Zachary Vorndran"
    },
    {
      "affiliations": [
        "Cabaletta Bio, Philadelphia, USA"
      ],
      "name": "Alexandra Ellis"
    },
    {
      "affiliations": [
        "Cabaletta Bio, Philadelphia, USA"
      ],
      "name": "Jazmean Williams"
    },
    {
      "affiliations": [
        "Cabaletta Bio, Philadelphia, USA"
      ],
      "name": "Steve Flanagan"
    },
    {
      "affiliations": [
        "Cabaletta Bio, Philadelphia, USA"
      ],
      "name": "Quynh Lam"
    },
    {
      "affiliations": [
        "Cabaletta Bio, Philadelphia, USA"
      ],
      "name": "Domenick Braccia"
    },
    {
      "affiliations": [
        "Cabaletta Bio, Philadelphia, USA"
      ],
      "name": "Fatemeh Hadi-Nezhad"
    },
    {
      "affiliations": [
        "Cabaletta Bio, Philadelphia, USA"
      ],
      "name": "Dan Thompson"
    },
    {
      "affiliations": [
        "Cabaletta Bio, Philadelphia, USA"
      ],
      "name": "Raj Tummala"
    },
    {
      "affiliations": [
        "Cabaletta Bio, Philadelphia, USA"
      ],
      "name": "Samik Basu"
    },
    {
      "affiliations": [
        "Cabaletta Bio, Philadelphia, USA"
      ],
      "name": "David Chang"
    }
  ],
  "title": "P.257 Reset-SSc: clinical trial evaluating rese-cel (resecabtagene autoleucel), a fully human, autologous 4-1BB CD19-CAR T cell therapy in systemic sclerosis",
  "uid": "1e81e017-997b-577d-ae60-634a26c057c5"
}