{
  "abstract": "Background Adoptive cell therapy (ACT) using ex vivo-expanded autologous tumor-infiltrating lymphocytes (TILs) has shown the potential to induce long-lasting remissions in melanoma. Recent clinical trials have validated the efficacy of TIL-ACT, leading its regulatory approval for patients with metastatic melanoma after failure of first-line immune checkpoint inhibitors. While high-dose interleukin-2 (IL-2) enhances efficacy, it is associated with considerable toxicity such as fever/chills, hypotension and pulmonary complications. Moreover, IL-2 may expand regulatory T cells (Tregs) through its high-affinity α-receptor, potentially limiting efficacy. ANV419, an IL-2 variant selective for the IL-2 receptor β/γ chains, preferentially targets effector T and NK cells, offering extended half-life and an improved safety profile.Methods The BaseTIL-03M trial ( NCT05869539) is a phase I study evaluating the safety and preliminary efficacy of combining TIL-ACT with ANV419 in patients with metastatic cutaneous melanoma refractory to standard systemic therapies. Ten patients received TILs in combination with ANV419 (243 mcg/kg) administered on the day of TIL transfer and again 14 days later. Prior to TIL infusion, patients underwent lymphodepletion with cyclophosphamide and fludarabine. The primary endpoint was safety within the first 30 days post-TIL infusion. Secondary endpoints included overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). In parallel, extensive translational studies of T cells blood and tumor tissues are underway.Results All ten patients were enrolled between June 2023 and May 2025. No dose-limiting toxicities were observed. Full safety data, ORR, and interim analyses of PFS and OS for the cohort will be presented at the meeting. Additionally, findings from translational studies including T cell repertoire profiling, single-cell proteomics of the TIL products and peripheral blood, and multiplex tissue imaging before and after treatment will be shared.Conclusions The BaseTIL-03M trial demonstrates that combining TIL-ACT with ANV419 is feasible and well tolerated, with no dose-limiting toxicities observed and preliminary signals of clinical benefit. These encouraging findings support advancement to a phase II trial focused on efficacy, to be conducted with the PragmaTIL network.Trial Registration Clinical TrialsGov: NCT05869539Ethics Approval All patients were consented and signed the ICF before being included in the trial.Consent Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.",
  "authors": [
    {
      "affiliations": [
        "University Hospital of Basel, Basel, BS, Switzerland"
      ],
      "name": "David Koenig"
    },
    {
      "affiliations": [
        "University Hospital of Basel, Basel, BS, Switzerland"
      ],
      "name": "Julia Lehmann"
    },
    {
      "affiliations": [
        "University Hospital of Basel, Basel, BS, Switzerland"
      ],
      "name": "Philippe Caloba"
    },
    {
      "affiliations": [
        "University Hospital of Basel, Basel, BS, Switzerland"
      ],
      "name": "Helen Thut"
    },
    {
      "affiliations": [
        "University Hospital of Basel, Basel, BS, Switzerland"
      ],
      "name": "Andreas Zingg"
    },
    {
      "affiliations": [
        "University Hospital of Basel, Basel, BS, Switzerland"
      ],
      "name": "Andreas Schmitt"
    },
    {
      "affiliations": [
        "University Hospital of Basel, Basel, BS, Switzerland"
      ],
      "name": "Michael Sandholzer"
    },
    {
      "affiliations": [
        "University Hospital of Basel, Basel, BS, Switzerland"
      ],
      "name": "Sarp Uzun"
    },
    {
      "affiliations": [
        "University Hospital of Basel, Basel, BS, Switzerland"
      ],
      "name": "Natalia Rodrigues Mantuano"
    },
    {
      "affiliations": [
        "University Hospital of Basel, Basel, BS, Switzerland"
      ],
      "name": "Benjamin Kasenda"
    },
    {
      "affiliations": [
        "University Hospital of Basel, Basel, BS, Switzerland"
      ],
      "name": "Katharina Glatz"
    },
    {
      "affiliations": [
        "University Hospital of Basel, Basel, BS, Switzerland"
      ],
      "name": "Matthias Matter"
    },
    {
      "affiliations": [
        "University Hospital of Basel, Basel, BS, Switzerland"
      ],
      "name": "Jana van den Berg"
    },
    {
      "affiliations": [
        "University Hospital of Basel, Basel, BS, Switzerland"
      ],
      "name": "Andreas Holbro"
    },
    {
      "affiliations": [
        "University Hospital of Basel, Basel, BS, Switzerland"
      ],
      "name": "Nina Khanna"
    },
    {
      "affiliations": [
        "University Hospital of Basel, Basel, BS, Switzerland"
      ],
      "name": "Lukas Jeker"
    },
    {
      "affiliations": [
        "University Hospital of Basel, Basel, BS, Switzerland"
      ],
      "name": "Jörg Halter"
    },
    {
      "affiliations": [
        "University Hospital of Basel, Basel, BS, Switzerland"
      ],
      "name": "Mascha Binder"
    },
    {
      "affiliations": [
        "University Hospital of Basel, Basel, BS, Switzerland"
      ],
      "name": "Alfred Zippelius"
    },
    {
      "affiliations": [
        "University Hospital of Basel, Basel, BS, Switzerland"
      ],
      "name": "Heinz Läubli"
    }
  ],
  "title": "374 Combination of adoptive cell transfer with β/γ-specific interleukin-2 therapy",
  "uid": "46dba0a2-5f95-515a-9387-bf82ecb34351"
}