Adoptive cell therapy with tumor-infiltrating lymphocytes in combination with nivolumab in patients with advanced melanoma

作者：David König, Benjamin Kasenda, Michael T. Sandholzer, Alin Chirindel, Andreas Zingg, Reto Ritschard, Helen Thut, Katharina Glatz, Elisabeth A. Kappos, Dirk J. Schaefer, Christoph Kettelhack, Jakob Robert Passweg, Katharina Baur, Andreas Holbro, Andreas S. Buser, Didier Lardinois, Lukas T. Jeker, Nina Khanna, Frank Stenner, Matthias Sebastian Matter, Natália Rodrigues Mantuano, Mascha Binder, A. Zippelius, Heinz Läubli · 发表于：Immuno-Oncology Technology · 年份：2024 · DOI：10.1016/j.iotech.2024.100728 · 被引用次数：13 · 研究领域：CAR-T cell therapy research、Cancer Research and Treatments、Immunotherapy and Immune Responses

Background Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) is a personalized immunotherapy. The efficacy of TIL-ACT has been demonstrated prospectively in patients with advanced melanoma but is not limited to melanoma patients. Many patients are refractory to TIL-ACT, however, or their cancer becomes resistant. Combining anti-programmed cell death protein 1 (anti-PD-1) with TIL-ACT to antagonize the immunosuppressive tumor microenvironment may synergize to enhance the antitumor potential. Material and methods We set up the BaseTIL trial (NCT04165967), a single-center investigator-initiated phase I trial, to test feasibility and safety of TIL-ACT followed by PD-1 blockade in patients with advanced cutaneous melanoma with disease progression after at least one line of anti-PD-1. TIL-ACT included tumor collection, ex vivo TIL expansion, lymphodepletion with cyclophosphamide and fludarabine, TIL transfer, and in vivo TIL stimulation with interleukin 2 (125 000 IU/kg, 10 days). TIL-ACT was followed by nivolumab treatment for a maximum of 2 years. Nine patients were planned for inclusion. Results Between 2020 and 2022, we enrolled 11 patients and 9 underwent a TIL transfer (median transfused cell number: 66.25 × 10 9 ). Two patients did not start lymphodepletion. Nine patients received at least 1 dose of interleukin 2 (median number: 10; range, 1-10), seven started nivolumab (median number: 5; range, 2-23). All patients had hematologic adverse events (AEs). Mo...