TY - JOUR T1 - Tumor infiltrating lymphocytes (TIL) therapy in metastatic melanoma: boosting of neoantigen-specific T cell reactivity and long-term follow-up JF - Journal for ImmunoTherapy of Cancer JO - J Immunother Cancer DO - 10.1136/jitc-2020-000848 VL - 8 IS - 2 SP - e000848 AU - Joost H van den Berg AU - Bianca Heemskerk AU - Nienke van Rooij AU - Raquel Gomez-Eerland AU - Samira Michels AU - Maaike van Zon AU - Renate de Boer AU - Noor A M Bakker AU - Annelies Jorritsma-Smit AU - Marit M van Buuren AU - Pia Kvistborg AU - Hergen Spits AU - Remko Schotte AU - Henk Mallo AU - Matthias Karger AU - Joris A van der Hage AU - Michel W J M Wouters AU - Loes M Pronk AU - Marnix H Geukes Foppen AU - Christian U Blank AU - Jos H Beijnen AU - Bastiaan Nuijen AU - Ton N Schumacher AU - John B A G Haanen Y1 - 2020/08/01 UR - http://jitc.bmj.com/content/8/2/e000848.abstract N2 - Treatment of metastatic melanoma with autologous tumor infiltrating lymphocytes (TILs) is currently applied in several centers. Robust and remarkably consistent overall response rates, of around 50% of treated patients, have been observed across hospitals, including a substantial fraction of durable, complete responses.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. ER -