Scalable expansion of potent genetically modified human langerhans cells in a closed system for clinical applications Journal Article

Authors: Yuan, J.; Kendle, R.; Ireland, J.; Heller, G.; Sadelain, M.; Young, J. W.; Riviere, I.
Article Title: Scalable expansion of potent genetically modified human langerhans cells in a closed system for clinical applications
Abstract: The administration of dendritic cell vaccines is a promising approach for cancer immunotherapy. Langerhans cells (LCs) that are genetically modified to express viral or tumor antigens are a dendritic cell subset of particular interest because they elicit potent antigen-specific immune responses. For clinical investigation, transduced, functional LCs must be generated in sufficient numbers using a scalable closed system that conforms to current good manufacturing practices. We therefore developed a process to expand CD34 hematopoietic progenitor cell-derived LCs in serum-free medium using hydrophobic culture bags and compared their biologic function to that of LCs grown in plates or flasks. We obtained significantly higher yields of mature LCs in bags compared with plates or flasks. LCs grown in bags displayed comparable maturation phenotypes and were transduced by GaLV-pseudotyped retroviral vectors with the same efficiency as LCs grown in plates or flasks. Bag-expanded LCs effectively stimulated the proliferation of allogeneic T lymphocytes and the production of interferon-γ by autologous CD8 T cells against the viral influenza matrix peptide or human tyrosinase. We have thus developed a scalable closed process to expand genetically modified, biologically functional CD34 hematopoietic progenitor cell-derived LCs for phase I clinical trials. © 2007 Lippincott Williams & Wilkins, Inc.
Keywords: controlled study; human cell; antigen expression; cd8+ t lymphocyte; cell proliferation; lymphocyte proliferation; t lymphocyte; dendritic cell vaccine; cancer immunotherapy; dendritic cell; tumor antigen; transduction, genetic; lymphocyte activation; cytokines; dendritic cells; lymphocyte culture test, mixed; cryopreservation; dna modification; immune response; immunotherapy; gamma interferon; peptide fragments; t-lymphocytes, cytotoxic; retrovirus vector; hematopoietic stem cells; cell culture techniques; virus antigen; hematopoietic stem cell; monophenol monooxygenase; antigens, cd34; cd34 selection; viral matrix proteins; expansion; langerhans cell; langerhans cells; interferon production; apc function; closed system; good manufacturing practice
Journal Title: Journal of Immunotherapy
Volume: 30
Issue: 6
ISSN: 1524-9557
Publisher: Lippincott Williams & Wilkins  
Date Published: 2007-09-01
Start Page: 634
End Page: 643
Language: English
DOI: 10.1097/CJI.0b013e31804efc8b
PUBMED: 17667527
PROVIDER: scopus
Notes: --- - "Cited By (since 1996): 3" - "Export Date: 17 November 2011" - "CODEN: JOIME" - "Source: Scopus"