RT Journal Article
SR Electronic
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
FD BMJ Publishing Group Ltd
SP e000848
DO 10.1136/jitc-2020-000848
VO 8
IS 2
A1 Joost H van den Berg
A1 Bianca Heemskerk
A1 Nienke van Rooij
A1 Raquel Gomez-Eerland
A1 Samira Michels
A1 Maaike van Zon
A1 Renate de Boer
A1 Noor A M Bakker
A1 Annelies Jorritsma-Smit
A1 Marit M van Buuren
A1 Pia Kvistborg
A1 Hergen Spits
A1 Remko Schotte
A1 Henk Mallo
A1 Matthias Karger
A1 Joris A van der Hage
A1 Michel W J M Wouters
A1 Loes M Pronk
A1 Marnix H Geukes Foppen
A1 Christian U Blank
A1 Jos H Beijnen
A1 Bastiaan Nuijen
A1 Ton N Schumacher
A1 John B A G Haanen
YR 2020
UL http://jitc.bmj.com/content/8/2/e000848.abstract
AB 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.