Simplified protocol for clinical-grade tumor-infiltrating lymphocyte manufacturing with use of the Wave bioreactor.

Objective: 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.