Van den Berg et al. report the long-term clinical outcome and neoantigen specificity of autologous tumor infiltrating lymphocyte (TIL) therapy in 10 patients with anti-PD-1-naive metastatic melanoma based on a phase I/II study. Two patients achieved complete responses for over 7 years, 3 achieved partial responses, and 1 had stable disease for 2 months. TIL infusion products analyzed from 3 responding patients had detectable levels of neoantigen-reactive T cells; 6 out of 9 of these increased post infusion in peripheral blood, and neoantigen-specific T cells were detectable in peripheral blood at low levels up to 3 years post infusion.
Contributed by Shishir Pant
ABSTRACT: 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 nave 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.
Author Info: (1) BioTherapeutics Unit, Netherlands Cancer Institute, Amsterdam, The Netherlands. (2) Division of Molecular Oncology and Immunology, Netherlands Cancer Institute, Amsterdam, The
Author Info: (1) BioTherapeutics Unit, Netherlands Cancer Institute, Amsterdam, The Netherlands. (2) Division of Molecular Oncology and Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands. (3) Division of Molecular Oncology and Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands. (4) Division of Molecular Oncology and Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands. (5) Division of Molecular Oncology and Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands. (6) BioTherapeutics Unit, Netherlands Cancer Institute, Amsterdam, The Netherlands. (7) BioTherapeutics Unit, Netherlands Cancer Institute, Amsterdam, The Netherlands. (8) BioTherapeutics Unit, Netherlands Cancer Institute, Amsterdam, The Netherlands. (9) Division of Molecular Oncology and Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands. (10) Division of Molecular Oncology and Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands. (11) Division of Molecular Oncology and Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands. (12) AIMM Therapeutics, Amsterdam, The Netherlands. Experimental Immunology, Amsterdam University Medical Centres, Amsterdam, Noord-Holland, The Netherlands. (13) AIMM Therapeutics, Amsterdam, The Netherlands. (14) Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands. (15) Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands. (16) Department of Surgery, Leiden Universitair Medisch Centrum, Leiden, Zuid-Holland, The Netherlands. (17) Surgical Oncology, Antoni van Leeuwenhoek Nederlands Kanker Instituut, Amsterdam, The Netherlands. Dutch Institute for Clinical Auditing, Leiden, The Netherlands. (18) Department of Biometrics, Netherlands Cancer Institute, Amsterdam, The Netherlands. (19) Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands. (20) Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, Noord-Holland, The Netherlands. (21) Department of Pharmacy & Pharmacology, Netherlands Cancer Institute, Amsterdam, The Netherlands. Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University Department of Pharmaceutical Sciences, Utrecht, Utrecht, The Netherlands. (22) Department of Pharmacy & Pharmacology, Netherlands Cancer Institute, Amsterdam, The Netherlands. (23) Division of Molecular Oncology and Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands. Oncode Institute, Utrecht, The Netherlands. (24) Division of Molecular Oncology and Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands j.haanen@nki.nl.
