TY - JOUR
T1 - Tumor infiltrating lymphocytes (TIL) therapy in metastatic melanoma: Boosting of neoantigen-specific T cell reactivity and long-term follow-up
AU - van den Berg, Joost H.
AU - Heemskerk, Bianca
AU - van Rooij, Nienke
AU - Gomez-Eerland, Raquel
AU - Michels, Samira
AU - van Zon, Maaike
AU - de Boer, Renate
AU - Bakker, Noor A. M.
AU - Jorritsma-Smit, Annelies
AU - van Buuren, Marit M.
AU - Kvistborg, Pia
AU - Spits, Hergen
AU - Schotte, Remko
AU - Mallo, Henk
AU - Karger, Matthias
AU - van der Hage, Joris A.
AU - Wouters, Michel W. J. M.
AU - Pronk, Loes M.
AU - Geukes Foppen, Marnix H.
AU - Blank, Christian U.
AU - Beijnen, Jos H.
AU - Nuijen, Bastiaan
AU - Schumacher, Ton N.
AU - Haanen, John B. A. G.
PY - 2020/8/4
Y1 - 2020/8/4
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.
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.
KW - immunotherapy, adoptive
KW - lymphocytes, tumor-infiltrating
KW - melanoma
UR - http://www.scopus.com/inward/record.url?scp=85089131980&partnerID=8YFLogxK
U2 - https://doi.org/10.1136/jitc-2020-000848
DO - https://doi.org/10.1136/jitc-2020-000848
M3 - Article
C2 - 32753545
SN - 2051-1426
VL - 8
JO - Journal for Immunotherapy of Cancer
JF - Journal for Immunotherapy of Cancer
IS - 2
M1 - e000848
ER -