Tumor infiltrating lymphocytes (TIL) therapy in metastatic melanoma: boosting of neoantigen-specific T cell reactivity and long-term follow-up

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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Main Authors: 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
Format: Article
Language:English
Published: BMJ Publishing Group 2020-10-01
Series:Journal for ImmunoTherapy of Cancer
Online Access:https://jitc.bmj.com/content/8/2/e000848.full
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Summary: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.
ISSN:2051-1426

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