Adoptive cell therapy with tumor-infiltrating lymphocytes in combination with nivolumab in patients with advanced melanoma
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,...
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Elsevier
2024-12-01
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| author | D. König B. Kasenda M. Sandholzer A. Chirindel A. Zingg R. Ritschard H. Thut K. Glatz E.A. Kappos D. Schaefer C. Kettelhack J. Passweg K. Baur A. Holbro A. Buser D. Lardinois L.T. Jeker N. Khanna F. Stenner M.S. Matter N. Rodrigues Mantuano M. Binder A. Zippelius H. Läubli |
| author_facet | D. König B. Kasenda M. Sandholzer A. Chirindel A. Zingg R. Ritschard H. Thut K. Glatz E.A. Kappos D. Schaefer C. Kettelhack J. Passweg K. Baur A. Holbro A. Buser D. Lardinois L.T. Jeker N. Khanna F. Stenner M.S. Matter N. Rodrigues Mantuano M. Binder A. Zippelius H. Läubli |
| author_sort | D. König |
| collection | DOAJ |
| description | 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 × 109). 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). Most common non-hematologic AEs were fever and cytokine release syndrome. No nivolumab-associated AEs of ≥ grade 2 occurred. The objective response rate to TIL-ACT was 22% (2/9, 2 partial remission). Conclusions: TIL-ACT with nivolumab is feasible and safe. Larger trials are needed to further determine the efficacy of this combination. |
| format | Article |
| id | doaj-art-a77a15df7af5480ea93dda0ce4aa25e6 |
| institution | DOAJ |
| issn | 2590-0188 |
| language | English |
| publishDate | 2024-12-01 |
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| series | Immuno-Oncology and Technology |
| spelling | doaj-art-a77a15df7af5480ea93dda0ce4aa25e62025-08-20T02:52:16ZengElsevierImmuno-Oncology and Technology2590-01882024-12-012410072810.1016/j.iotech.2024.100728Adoptive cell therapy with tumor-infiltrating lymphocytes in combination with nivolumab in patients with advanced melanomaD. König0B. Kasenda1M. Sandholzer2A. Chirindel3A. Zingg4R. Ritschard5H. Thut6K. Glatz7E.A. Kappos8D. Schaefer9C. Kettelhack10J. Passweg11K. Baur12A. Holbro13A. Buser14D. Lardinois15L.T. Jeker16N. Khanna17F. Stenner18M.S. Matter19N. Rodrigues Mantuano20M. Binder21A. Zippelius22H. Läubli23Department of Biomedicine, University of Basel, Basel, Switzerland; Division of Medical Oncology, University Hospital Basel, Basel, Switzerland; Innovation Focus Cell Therapies, University Hospital Basel, Basel, SwitzerlandDivision of Medical Oncology, University Hospital Basel, Basel, Switzerland; Innovation Focus Cell Therapies, University Hospital Basel, Basel, SwitzerlandDepartment of Biomedicine, University of Basel, Basel, SwitzerlandDepartment of Radiology and Nuclear Medicine, University Hospital Basel, Basel, SwitzerlandDepartment of Biomedicine, University of Basel, Basel, SwitzerlandDepartment of Biomedicine, University of Basel, Basel, Switzerland; Innovation Focus Cell Therapies, University Hospital Basel, Basel, SwitzerlandDepartment of Biomedicine, University of Basel, Basel, Switzerland; Innovation Focus Cell Therapies, University Hospital Basel, Basel, SwitzerlandInstitute of Pathology and Medical Genetics, University Hospital Basel, Basel, SwitzerlandDepartment of Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital Basel, Basel, SwitzerlandDepartment of Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital Basel, Basel, SwitzerlandVisceral Surgery, Clarunis University Center for Gastrointestinal and Liver Disease, University Hospital Basel and St. Claraspital Basel, Basel, SwitzerlandInnovation Focus Cell Therapies, University Hospital Basel, Basel, Switzerland; Division of Hematology, University Hospital Basel, Basel, SwitzerlandInnovation Focus Cell Therapies, University Hospital Basel, Basel, Switzerland; Division of Hematology, University Hospital Basel, Basel, SwitzerlandInnovation Focus Cell Therapies, University Hospital Basel, Basel, Switzerland; Division of Hematology, University Hospital Basel, Basel, Switzerland; Blood Donation Center, Basel, SwitzerlandInnovation Focus Cell Therapies, University Hospital Basel, Basel, Switzerland; Division of Hematology, University Hospital Basel, Basel, Switzerland; Blood Donation Center, Basel, SwitzerlandDepartment of Thoracic Surgery, University Hospital Basel, Basel, SwitzerlandDepartment of Biomedicine, University of Basel, Basel, Switzerland; Innovation Focus Cell Therapies, University Hospital Basel, Basel, Switzerland; Division of Transplantation Immunology and Nephrology, University Hospital Basel, Basel, SwitzerlandDepartment of Biomedicine, University of Basel, Basel, Switzerland; Innovation Focus Cell Therapies, University Hospital Basel, Basel, Switzerland; Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, SwitzerlandDivision of Medical Oncology, University Hospital Basel, Basel, SwitzerlandInstitute of Pathology and Medical Genetics, University Hospital Basel, Basel, SwitzerlandDepartment of Biomedicine, University of Basel, Basel, SwitzerlandDepartment of Biomedicine, University of Basel, Basel, Switzerland; Division of Medical Oncology, University Hospital Basel, Basel, SwitzerlandDepartment of Biomedicine, University of Basel, Basel, Switzerland; Division of Medical Oncology, University Hospital Basel, Basel, Switzerland; Innovation Focus Cell Therapies, University Hospital Basel, Basel, SwitzerlandDepartment of Biomedicine, University of Basel, Basel, Switzerland; Division of Medical Oncology, University Hospital Basel, Basel, Switzerland; Innovation Focus Cell Therapies, University Hospital Basel, Basel, Switzerland; Correspondence to: Prof. Dr Heinz Läubli, Division of Medical Oncology, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland. Tel: +41-61-265-50-74Background: 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 × 109). 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). Most common non-hematologic AEs were fever and cytokine release syndrome. No nivolumab-associated AEs of ≥ grade 2 occurred. The objective response rate to TIL-ACT was 22% (2/9, 2 partial remission). Conclusions: TIL-ACT with nivolumab is feasible and safe. Larger trials are needed to further determine the efficacy of this combination.http://www.sciencedirect.com/science/article/pii/S259001882400025Xmelanomaadoptive cell therapytumor-infiltrating lymphocytesnivolumabphase I trial |
| spellingShingle | D. König B. Kasenda M. Sandholzer A. Chirindel A. Zingg R. Ritschard H. Thut K. Glatz E.A. Kappos D. Schaefer C. Kettelhack J. Passweg K. Baur A. Holbro A. Buser D. Lardinois L.T. Jeker N. Khanna F. Stenner M.S. Matter N. Rodrigues Mantuano M. Binder A. Zippelius H. Läubli Adoptive cell therapy with tumor-infiltrating lymphocytes in combination with nivolumab in patients with advanced melanoma Immuno-Oncology and Technology melanoma adoptive cell therapy tumor-infiltrating lymphocytes nivolumab phase I trial |
| title | Adoptive cell therapy with tumor-infiltrating lymphocytes in combination with nivolumab in patients with advanced melanoma |
| title_full | Adoptive cell therapy with tumor-infiltrating lymphocytes in combination with nivolumab in patients with advanced melanoma |
| title_fullStr | Adoptive cell therapy with tumor-infiltrating lymphocytes in combination with nivolumab in patients with advanced melanoma |
| title_full_unstemmed | Adoptive cell therapy with tumor-infiltrating lymphocytes in combination with nivolumab in patients with advanced melanoma |
| title_short | Adoptive cell therapy with tumor-infiltrating lymphocytes in combination with nivolumab in patients with advanced melanoma |
| title_sort | adoptive cell therapy with tumor infiltrating lymphocytes in combination with nivolumab in patients with advanced melanoma |
| topic | melanoma adoptive cell therapy tumor-infiltrating lymphocytes nivolumab phase I trial |
| url | http://www.sciencedirect.com/science/article/pii/S259001882400025X |
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