Abstract CT032: Adoptive T cell transfer combined with DC vaccination in patients with metastatic melanoma
Authors: wickström stina L. , Lövgren Tanja , Wolodarski Maria , Edbäck Ulrika , Martell Eva , Markland Karin , Nyström Maria , Lundqvist Andreas , Jacobsson Hans , Hansson Johan , Masucci Giuseppe , Tell Roger , Poschke Isabel , Adamson Lars , Mattsson Jonas , Kiessling Rolf 
Published: August 2018

Background and aim: Although several drugs have been approved that improve overall survival in patients with metastatic melanoma, there is still a need for additional treatments when the approved ones are exhausted. Adoptive T-cell therapy (ACT) has been reported to induce clinical responses in up to 70% of stage IV melanoma patients. The aim of the MAT02 trial is to investigate the toxicity and feasibility of a combined treatment with adoptive transfer of autologous, tumor-derived T cells with or without autologous dendritic cell (DC) vaccination in patients with stage III/IV melanoma.

Method: This study is a single centre, open-label, two-armed, phase I trial. Five patients are assigned to each cohort (A or B) and receive ACT of autologous tumor infiltrating lymphocytes (TIL) without (A) or with (B) autologous tumor loaded DC i.c. Prior to TIL cell transfer, all patients are pre-treated with a precondition regimen. Administration of TIL cells is followed by IL-2 administration (100000 U/Kg q8hx14). Radiological evaluation is performed four weeks after the last DC administration. The primary objective is to evaluate the toxicity and feasibility. The secondary objectives are to generate large numbers of T cells, boost tumor-reactive T cells by DC vaccination, characterize the T cell population used for adoptive transfer with regard to phenotype and functionality, and generate an objective anti-tumour response.

Results: Cohort A in which patients received only TIL has been completed and the treatment was feasible with limited expected toxicity. All treated patients showed a mixed response or stable disease. However, these responses were not durable. The overall survival ranged between 4-17 months. For cohort B which received the combined treatment of TIL and DC vaccine, three patients have completed the treatment that has been feasible with limited expected toxicity. The number of cells transfused in this cohort ranged between 29 and 33 billion and all patients have been administered five DC-vaccinations. All 3 patients responded; one with a complete response which is still ongoing (&gt; 12 mo). Two patients showed a partial response, one with a long lasting response (&gt; 18 mo) and one with a short response (&lt; 4 mo). The accrual continues and we expect to include another two patients before the summer of 2018.

Conclusions: Adoptive T cell therapy combined with DC vaccination is safe with tolerable toxicity profiles and can result in complete clinical response in patients who have failed on checkpoint therapy.

Citation Format: stina L. wickström, Tanja Lövgren, Maria Wolodarski, Ulrika Edbäck, Eva Martell, Karin Markland, Maria Nyström, Andreas Lundqvist, Hans Jacobsson, Johan Hansson, Giuseppe Masucci, Roger Tell, Isabel Poschke, Lars Adamson, Jonas Mattsson, Rolf Kiessling. Adoptive T cell transfer combined with DC vaccination in patients with metastatic melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT032.