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

Publication ,  Journal Article
Klapper, JA; Thomasian, AA; Smith, DM; Gorgas, GC; Wunderlich, JR; Smith, FO; Hampson, BS; Rosenberg, SA; Dudley, ME
Published in: J Immunol Methods
June 30, 2009

Adoptive cell therapy (ACT) for metastatic melanoma involves the ex vivo expansion and reinfusion 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.

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Published In

J Immunol Methods

DOI

EISSN

1872-7905

Publication Date

June 30, 2009

Volume

345

Issue

1-2

Start / End Page

90 / 99

Location

Netherlands

Related Subject Headings

  • Phenotype
  • Perfusion
  • Lymphocytes, Tumor-Infiltrating
  • Immunotherapy, Adoptive
  • Immunology
  • Humans
  • Culture Media
  • Cells, Cultured
  • Cell Survival
  • Cell Culture Techniques
 

Citation

APA
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MLA
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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. J Immunol Methods, 345(1–2), 90–99. https://doi.org/10.1016/j.jim.2009.04.009
Klapper, Jacob A., Armen A. Thomasian, Douglas M. Smith, Gayle C. Gorgas, John R. Wunderlich, Franz O. Smith, Brian S. Hampson, Steven A. Rosenberg, and Mark E. Dudley. “Single-pass, closed-system rapid expansion of lymphocyte cultures for adoptive cell therapy.J Immunol Methods 345, no. 1–2 (June 30, 2009): 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. J Immunol Methods. 2009 Jun 30;345(1–2):90–9.
Klapper, Jacob A., et al. “Single-pass, closed-system rapid expansion of lymphocyte cultures for adoptive cell therapy.J Immunol Methods, vol. 345, no. 1–2, June 2009, pp. 90–99. Pubmed, doi:10.1016/j.jim.2009.04.009.
Klapper JA, Thomasian AA, Smith DM, Gorgas GC, Wunderlich JR, Smith FO, Hampson BS, Rosenberg SA, Dudley ME. Single-pass, closed-system rapid expansion of lymphocyte cultures for adoptive cell therapy. J Immunol Methods. 2009 Jun 30;345(1–2):90–99.
Journal cover image

Published In

J Immunol Methods

DOI

EISSN

1872-7905

Publication Date

June 30, 2009

Volume

345

Issue

1-2

Start / End Page

90 / 99

Location

Netherlands

Related Subject Headings

  • Phenotype
  • Perfusion
  • Lymphocytes, Tumor-Infiltrating
  • Immunotherapy, Adoptive
  • Immunology
  • Humans
  • Culture Media
  • Cells, Cultured
  • Cell Survival
  • Cell Culture Techniques