3028 Background: TIL treatment holds the promise to introduce a new treatment paradigm into oncology practice. To demonstrate the logistical feasibility of this complex approach in Europe, at Herlev Hospital, Denmark, we have initiated a trial for patients with metastatic melanoma and evaluated the melanoma-specific immunity in the peripheral blood. Methods: We present the updated results of trial NCT00937625. The study takes place in a medium-size academic center (30 in-patient oncology beds) equipped with a 36 square meters cGMP cell production lab integrated in a hematopoietic stem cell transplantation unit. Patients were treated with autologous TILs preceded by standard lymphodepleting chemotherapy but followed by attenuated regimens of IL-2 (n=6 low-dose s.c. for 14 days; n=9 i.v. intermediate decrescendo dose). Melanoma-specific responses were assessed with intracellular cytokine staining. Results: We have generated TILs from 28/31 patients, with 15 patients treated so far and many TILs cryopreserved for future use. Patients were treated with an average of >50x10⁹ CD4⁺, CD8⁺and a small but consistent fraction of γδ TILs. The lower doses of IL-2 have significantly decreased the classical toxicity of the treatment associated with more harsh IL-2 regimens, and response evaluation showed the achievement of three CR lasting > 1 year and four PR. Clinical responses were associated with high numbers of tumour reactive T-cells infused. Importantly, in most responding patients we observed induction and durable persistence (up to 1 year) of anti-melanoma T-cell responses in the peripheral blood. Conclusions: A high response rate including durable complete responses can be induced after treatment with TILs followed by an attenuated regimen of IL-2, which significantly reduced the occurrence of severe side effects. Effective TIL treatment is associated with induction and long-term persistence in the blood of T cells producing in vitro anticancer responses. By showing that TIL-based ACT is logistically feasible and accessible to medium-size academic centers, we open the possibility for testing this treatment in a large randomized setting in Europe. Clinical trial information: NCT00937625.