Background aims: The high level of complexity of current Good Manufacturing Practice-compliant methods of manufacturing hampers rapid and broad application of treatment with tumor-infiltrating lymphocytes (TILs). Methods: To ensure higher applicability of TIL production to laboratory routine, a practical and simple protocol of TIL manufacturing with the use of a closed-system bioreactor was developed and implemented at our institution. Results: This protocol enabled significant work load reduction during the most labor-intense step of TIL expansion, and allowed generation of high-quality TIL products, which mediated clinical regression in patients with metastatic melanoma. Conclusions: Implementation of simplified methods of TIL expansion will speed up dissemination of TIL methods worldwide and will increase patient access to this highly effective treatment. ?? 2014 International Society for Cellular Therapy.