Tumor infiltrating lymphocytes (TIL) therapy in metastatic melanoma: boosting of neoantigen-specific T cell reactivity and long-term follow-up
Purpose Execute a phase I/II feasibility study with TIL therapy in metastatic melanoma at the Netherlands Cancer Institute, with the goal to assess feasibility and potential value of a randomized phase III trial.Experimental Ten patients were treated with TIL therapy. Infusion products and periphera...
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BMJ Publishing Group
2020-10-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/8/2/e000848.full |
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| author | Annelies Jorritsma-Smit Michel W J M Wouters Bianca Heemskerk Nienke van Rooij Pia Kvistborg John B A G Haanen Joost H van den Berg Raquel Gomez-Eerland Samira Michels Maaike van Zon Renate de Boer Noor A M Bakker Marit M van Buuren Hergen Spits Remko Schotte Henk Mallo Matthias Karger Joris A van der Hage Loes M Pronk Marnix H Geukes Foppen Christian U Blank Jos H Beijnen Bastiaan Nuijen Ton N Schumacher |
| author_facet | Annelies Jorritsma-Smit Michel W J M Wouters Bianca Heemskerk Nienke van Rooij Pia Kvistborg John B A G Haanen Joost H van den Berg Raquel Gomez-Eerland Samira Michels Maaike van Zon Renate de Boer Noor A M Bakker Marit M van Buuren Hergen Spits Remko Schotte Henk Mallo Matthias Karger Joris A van der Hage Loes M Pronk Marnix H Geukes Foppen Christian U Blank Jos H Beijnen Bastiaan Nuijen Ton N Schumacher |
| author_sort | Annelies Jorritsma-Smit |
| collection | DOAJ |
| description | Purpose Execute a phase I/II feasibility study with TIL therapy in metastatic melanoma at the Netherlands Cancer Institute, with the goal to assess feasibility and potential value of a randomized phase III trial.Experimental Ten patients were treated with TIL therapy. Infusion products and peripheral blood samples were phenotypically characterized and neoantigen reactivity was assessed. Here, we present long-term clinical outcome and translational data on neoantigen reactivity of the T cell products.Results Five out of 10 patients, who were all anti-PD-1 naïve at time of treatment, showed an objective clinical response, including two patients with a complete response that are both ongoing for more than 7 years. Immune monitoring demonstrated that neoantigen-specific T cells were detectable in TIL infusion products from three out of three patients analyzed. For six out of the nine neoantigen-specific T cell responses detected in these TIL products, T cell response magnitude increased significantly in the peripheral blood compartment after therapy, and neoantigen-specific T cells were detectable for up to 3 years after TIL infusion.Conclusion The clinical results from this study confirm the robustness of TIL therapy in metastatic melanoma and the potential role of neoantigen-specific T cell reactivity. In addition, the data from this study supported the rationale to initiate an ongoing multicenter phase III TIL trial. |
| format | Article |
| id | doaj-art-dcfa2791fafa4572a3dce6276ee8be68 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2020-10-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-dcfa2791fafa4572a3dce6276ee8be682024-11-10T05:25:07ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-10-018210.1136/jitc-2020-000848Tumor infiltrating lymphocytes (TIL) therapy in metastatic melanoma: boosting of neoantigen-specific T cell reactivity and long-term follow-upAnnelies Jorritsma-Smit0Michel W J M Wouters1Bianca Heemskerk2Nienke van Rooij3Pia Kvistborg4John B A G Haanen5Joost H van den Berg6Raquel Gomez-Eerland7Samira Michels8Maaike van Zon9Renate de Boer10Noor A M Bakker11Marit M van Buuren12Hergen Spits13Remko Schotte14Henk Mallo15Matthias Karger16Joris A van der Hage17Loes M Pronk18Marnix H Geukes Foppen19Christian U Blank20Jos H Beijnen21Bastiaan Nuijen22Ton N Schumacher233 Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center, Groningen, The Netherlands2 Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, The NetherlandsAff1 grid.430814.aNetherlands Cancer Institute NKI-AVL Amsterdam the NetherlandsAff1 grid.430814.aNetherlands Cancer Institute NKI-AVL Amsterdam the Netherlands1 Molecular Oncology & Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands2 Division of Molecular Oncology and Immunology, Netherlands Cancer Institute, Amsterdam, The NetherlandsDivision of Molecular Oncology & Immunology, The Netherlands Cancer Institute – Antoni van Leeuwenhoek, Amsterdam, The Netherlands2 Division of Molecular Oncology and Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands2 Division of Molecular Oncology and Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands1 BioTherapeutics Unit, Netherlands Cancer Institute, Amsterdam, The Netherlands1 BioTherapeutics Unit, Netherlands Cancer Institute, Amsterdam, The Netherlands1 BioTherapeutics Unit, Netherlands Cancer Institute, Amsterdam, The Netherlands2 Division of Molecular Oncology and Immunology, Netherlands Cancer Institute, Amsterdam, The NetherlandsExperimental Immunology, Amsterdam University Medical Centres, Amsterdam, The Netherlands1AIMM Therapeutics, Amsterdam, Netherlands5 Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands5 Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands6 Department of Surgery, Leiden Universitair Medisch Centrum, Leiden, Zuid-Holland, The Netherlands9 Department of Biometrics, Netherlands Cancer Institute, Amsterdam, The Netherlands5 Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands2 Division of Molecular Oncology and Immunology, The Netherlands Cancer Institute, Amsterdam, The NetherlandsDepartment of Pharmacy & Pharmacology, Netherlands Cancer Institute, Amsterdam, The NetherlandsDepartment of Pharmacy and Pharmacology, The Netherlands Cancer Institute – Antoni van Leeuwenhoek, Amsterdam, The Netherlands2 Division of Molecular Oncology and Immunology, Netherlands Cancer Institute, Amsterdam, The NetherlandsPurpose Execute a phase I/II feasibility study with TIL therapy in metastatic melanoma at the Netherlands Cancer Institute, with the goal to assess feasibility and potential value of a randomized phase III trial.Experimental Ten patients were treated with TIL therapy. Infusion products and peripheral blood samples were phenotypically characterized and neoantigen reactivity was assessed. Here, we present long-term clinical outcome and translational data on neoantigen reactivity of the T cell products.Results Five out of 10 patients, who were all anti-PD-1 naïve at time of treatment, showed an objective clinical response, including two patients with a complete response that are both ongoing for more than 7 years. Immune monitoring demonstrated that neoantigen-specific T cells were detectable in TIL infusion products from three out of three patients analyzed. For six out of the nine neoantigen-specific T cell responses detected in these TIL products, T cell response magnitude increased significantly in the peripheral blood compartment after therapy, and neoantigen-specific T cells were detectable for up to 3 years after TIL infusion.Conclusion The clinical results from this study confirm the robustness of TIL therapy in metastatic melanoma and the potential role of neoantigen-specific T cell reactivity. In addition, the data from this study supported the rationale to initiate an ongoing multicenter phase III TIL trial.https://jitc.bmj.com/content/8/2/e000848.full |
| spellingShingle | Annelies Jorritsma-Smit Michel W J M Wouters Bianca Heemskerk Nienke van Rooij Pia Kvistborg John B A G Haanen Joost H van den Berg Raquel Gomez-Eerland Samira Michels Maaike van Zon Renate de Boer Noor A M Bakker Marit M van Buuren Hergen Spits Remko Schotte Henk Mallo Matthias Karger Joris A van der Hage Loes M Pronk Marnix H Geukes Foppen Christian U Blank Jos H Beijnen Bastiaan Nuijen Ton N Schumacher Tumor infiltrating lymphocytes (TIL) therapy in metastatic melanoma: boosting of neoantigen-specific T cell reactivity and long-term follow-up Journal for ImmunoTherapy of Cancer |
| title | Tumor infiltrating lymphocytes (TIL) therapy in metastatic melanoma: boosting of neoantigen-specific T cell reactivity and long-term follow-up |
| title_full | Tumor infiltrating lymphocytes (TIL) therapy in metastatic melanoma: boosting of neoantigen-specific T cell reactivity and long-term follow-up |
| title_fullStr | Tumor infiltrating lymphocytes (TIL) therapy in metastatic melanoma: boosting of neoantigen-specific T cell reactivity and long-term follow-up |
| title_full_unstemmed | Tumor infiltrating lymphocytes (TIL) therapy in metastatic melanoma: boosting of neoantigen-specific T cell reactivity and long-term follow-up |
| title_short | Tumor infiltrating lymphocytes (TIL) therapy in metastatic melanoma: boosting of neoantigen-specific T cell reactivity and long-term follow-up |
| title_sort | tumor infiltrating lymphocytes til therapy in metastatic melanoma boosting of neoantigen specific t cell reactivity and long term follow up |
| url | https://jitc.bmj.com/content/8/2/e000848.full |
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