Development of an optimized closed and semi-automatic protocol for Good Manufacturing Practice manufacturing of tumor-infiltrating lymphocytes in a hospital environment

Abstract

Background aims: Several studies report on Good Manufacturing Process (GMP)-compliant manufacturing protocols for the ex vivo expansion of tumor-infiltrating lymphocytes (TILs) for the treatment of patients with refractory melanoma and other solid malignancies. Further opportunities for improvements in terms of ergonomy and operating time have been identified.

Methods: To enable GMP-compliant TILs production for adoptive cell therapy needs, a simple automated and reproducible protocol for TILs manufacturing with the use of a closed system was developed and implemented at the authors' institution.

Results: This protocol enabled significant operating time reduction during TILs expansion while allowing the generation of high-quality TILs products.

Conclusions: A simplified and efficient method of TILs expansion will enable the broadening of individualized tumor therapy and will increase patients' access to state-of-the-art TILs adoptive cell therapy treatment.

Keywords: Good Manufacturing Practice (GMP); Swissmedic; adoptive cell therapy (ACT); immunotherapy; manufacturing; tumor-infiltrating lymphocytes (TILs).