Single-pass, closed-system rapid expansion of lymphocyte cultures for adoptive cell therapy

Jacob A. Klapper, Armen A. Thomasian, Douglas M. Smith, Gayle C. Gorgas, John R. Wunderlich, Franz O. Smith, Brian S. Hampson, Steven A. Rosenberg, Mark E. Dudley

Research output: Contribution to journalArticle

Abstract

Adoptive cell therapy (ACT) for metastatic melanoma involves the ex vivo expansion and re-infusion of tumor infiltrating lymphocytes (TIL) obtained from resected specimens. With an overall objective response rate of 56%, this T-cell immunotherapy provides an appealing alternative to other therapies, including conventional therapies with lower response rates. However, there are significant regulatory and logistical concerns associated with the ex vivo activation and large-scale expansion of these cells. The best current practice uses a rapid expansion protocol (REP) consisting of an ex vivo process that occurs in tissue culture flasks (T-flasks) and gas-permeable bags, utilizes OKT3 (anti-CD3 monoclonal antibody), recombinant human interleukin-2, and irradiated peripheral blood mononuclear cells to initiate rapid lymphocyte growth. A major limitation to the widespread delivery of therapy to large numbers of melanoma patients is the open system in which a REP is initiated. To address this problem, we have investigated the initiation, expansion and harvest at clinical scale of TIL in a closed-system continuous perfusion bioreactor. Each cell product met all safety criteria for patient treatment and by head-to-head comparison had a similar potency and phenotype as cells grown in control T-flasks and gas-permeable bags. However, the currently available bioreactor cassettes were limited in the total cell numbers that could be generated. This bioreactor may simplify the process of the rapid expansion of TIL under stringent regulatory conditions thereby enabling other institutions to pursue this form of ACT.

Original languageEnglish (US)
Pages (from-to)90-99
Number of pages10
JournalJournal of Immunological Methods
Volume345
Issue number1-2
DOIs
StatePublished - Jun 30 2009
Externally publishedYes

Fingerprint

Cell- and Tissue-Based Therapy
Tumor-Infiltrating Lymphocytes
Bioreactors
Lymphocytes
Melanoma
Gases
Muromonab-CD3
Therapeutics
Patient Safety
Practice Guidelines
Immunotherapy
Interleukin-2
Blood Cells
Perfusion
Cell Count
Monoclonal Antibodies
T-Lymphocytes
Phenotype
Growth

Keywords

  • Adoptive cell therapy
  • Closed-system bioreactor
  • Rapid expansion
  • rhIL-2
  • Tumor infiltrating lymphocyte

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Klapper, J. A., Thomasian, A. A., Smith, D. M., Gorgas, G. C., Wunderlich, J. R., Smith, F. O., ... Dudley, M. E. (2009). Single-pass, closed-system rapid expansion of lymphocyte cultures for adoptive cell therapy. Journal of Immunological Methods, 345(1-2), 90-99. https://doi.org/10.1016/j.jim.2009.04.009

Single-pass, closed-system rapid expansion of lymphocyte cultures for adoptive cell therapy. / Klapper, Jacob A.; Thomasian, Armen A.; Smith, Douglas M.; Gorgas, Gayle C.; Wunderlich, John R.; Smith, Franz O.; Hampson, Brian S.; Rosenberg, Steven A.; Dudley, Mark E.

In: Journal of Immunological Methods, Vol. 345, No. 1-2, 30.06.2009, p. 90-99.

Research output: Contribution to journalArticle

Klapper, JA, Thomasian, AA, Smith, DM, Gorgas, GC, Wunderlich, JR, Smith, FO, Hampson, BS, Rosenberg, SA & Dudley, ME 2009, 'Single-pass, closed-system rapid expansion of lymphocyte cultures for adoptive cell therapy', Journal of Immunological Methods, vol. 345, no. 1-2, pp. 90-99. https://doi.org/10.1016/j.jim.2009.04.009
Klapper JA, Thomasian AA, Smith DM, Gorgas GC, Wunderlich JR, Smith FO et al. Single-pass, closed-system rapid expansion of lymphocyte cultures for adoptive cell therapy. Journal of Immunological Methods. 2009 Jun 30;345(1-2):90-99. https://doi.org/10.1016/j.jim.2009.04.009
Klapper, Jacob A. ; Thomasian, Armen A. ; Smith, Douglas M. ; Gorgas, Gayle C. ; Wunderlich, John R. ; Smith, Franz O. ; Hampson, Brian S. ; Rosenberg, Steven A. ; Dudley, Mark E. / Single-pass, closed-system rapid expansion of lymphocyte cultures for adoptive cell therapy. In: Journal of Immunological Methods. 2009 ; Vol. 345, No. 1-2. pp. 90-99.
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