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.
Center for Cancer Immune Therapy, Department of Hematology, Herlev, Denmark; Department of Oncology, Herlev Hospital, Herlev, Denmark; Department of Bio-medical Sciences, University of Catania, Italy. Electronic address: marco.donia@regionh.dk.
Marco
M
Donia
Center for Cancer Immune Therapy, Department of Hematology, Herlev, Denmark.
Signe Møllebæk
SM
Larsen
Center for Cancer Immune Therapy, Department of Hematology, Herlev, Denmark; Department of Oncology, Herlev Hospital, Herlev, Denmark.
Ozcan
O
Met
Center for Cancer Immune Therapy, Department of Hematology, Herlev, Denmark; Department of Oncology, Herlev Hospital, Herlev, Denmark. Electronic address: inge.marie.svane@regionh.dk.
Inge Marie
IM
Svane
D019149:Bioreactors; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D049109:Cell Proliferation / Q000235:genetics; D064987:Cell- and Tissue-Based Therapy; D006801:Humans; D016219:Immunotherapy, Adoptive; D016246:Lymphocytes, Tumor-Infiltrating / Q000166:cytology*; D008545:Melanoma / Q000473:pathology / Q000628:therapy*; D009362:Neoplasm Metastasis
Wave bioreactor; metastatic melanoma; rapid expansion; tumor-infiltrating lymphocytes