Rapid production of clinical-grade gammaretroviral vectors in expanded surface roller bottles using a "modified" step-filtration process for clearance of packaging cells

Steven A. Feldman, Stephanie L. Goff, Hui Xu, Mary A. Black, James N. Kochenderfer, Laura A. Johnson, James C. Yang, Qiong Wang, Maria R. Parkhurst, Scott Cross, Richard A. Morgan, Kenneth Cornetta, Steven A. Rosenberg

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Production of clinical-grade gammaretroviral vectors for ex vivo gene delivery requires a scalable process that can rapidly generate large amounts of vector supernatant, clear large numbers of residual packaging cells with minimal decreases in vector titer, and satisfy all current regulatory guidelines regarding product biosafety. To that end, we have developed a simplified method that is compliant with current good manufacturing practices for the production of clinical-grade gammaretroviral vectors in a clinical research environment. We validated a large-scale production platform utilizing 1,700-cm2 expanded surface roller bottles and a "modified" step-filtration process consisting of a 40/150-μm dual-screen filter for aggregate removal followed by a Sepacell 500II leukocyte reduction filter for removal of residual packaging cells. This clarification process can clear at least 2×10 9 viable producer cells using a single filter set-up without any significant loss of titer post-filtration. This platform typically generates 18 liters of vector supernatant to support small-scale clinical trials, but can easily be scaled up to 70 liters during a single manufacturing run. To date, this platform has generated five clinical-grade gammaretroviral vector products, four of which are now being used in adoptive cell therapy clinical trials for the treatment of a variety of solid cancers.

Original languageEnglish
Pages (from-to)107-115
Number of pages9
JournalHuman Gene Therapy
Volume22
Issue number1
DOIs
StatePublished - Jan 1 2011

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Product Packaging
Clinical Trials
Cell- and Tissue-Based Therapy
Leukocytes
Guidelines
Research
Genes
Neoplasms
Therapeutics

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Rapid production of clinical-grade gammaretroviral vectors in expanded surface roller bottles using a "modified" step-filtration process for clearance of packaging cells. / Feldman, Steven A.; Goff, Stephanie L.; Xu, Hui; Black, Mary A.; Kochenderfer, James N.; Johnson, Laura A.; Yang, James C.; Wang, Qiong; Parkhurst, Maria R.; Cross, Scott; Morgan, Richard A.; Cornetta, Kenneth; Rosenberg, Steven A.

In: Human Gene Therapy, Vol. 22, No. 1, 01.01.2011, p. 107-115.

Research output: Contribution to journalArticle

Feldman, SA, Goff, SL, Xu, H, Black, MA, Kochenderfer, JN, Johnson, LA, Yang, JC, Wang, Q, Parkhurst, MR, Cross, S, Morgan, RA, Cornetta, K & Rosenberg, SA 2011, 'Rapid production of clinical-grade gammaretroviral vectors in expanded surface roller bottles using a "modified" step-filtration process for clearance of packaging cells', Human Gene Therapy, vol. 22, no. 1, pp. 107-115. https://doi.org/10.1089/hum.2010.064
Feldman, Steven A. ; Goff, Stephanie L. ; Xu, Hui ; Black, Mary A. ; Kochenderfer, James N. ; Johnson, Laura A. ; Yang, James C. ; Wang, Qiong ; Parkhurst, Maria R. ; Cross, Scott ; Morgan, Richard A. ; Cornetta, Kenneth ; Rosenberg, Steven A. / Rapid production of clinical-grade gammaretroviral vectors in expanded surface roller bottles using a "modified" step-filtration process for clearance of packaging cells. In: Human Gene Therapy. 2011 ; Vol. 22, No. 1. pp. 107-115.
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