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

Cytotherapy. 2014 Aug;16(8):1117-20. doi: 10.1016/j.jcyt.2014.02.004. Epub 2014 May 13.


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.

Keywords: Wave bioreactor; metastatic melanoma; rapid expansion; tumor-infiltrating lymphocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bioreactors
  • CD8-Positive T-Lymphocytes / cytology*
  • Cell Proliferation / genetics
  • Cell- and Tissue-Based Therapy*
  • Humans
  • Immunotherapy, Adoptive*
  • Lymphocytes, Tumor-Infiltrating / cytology*
  • Melanoma / pathology
  • Melanoma / therapy*
  • Neoplasm Metastasis