Clinical grade OK432-activated dendritic cells: In vitro characterization and tracking during intralymphatic delivery

Emma West, Ruth Morgan, Karen Scott, Alison Merrick, Anatole Lubenko, David Pawson, Peter Selby, Paul Hatfield, Robin Prestwich, Sheila Fraser, David Eves, Alan Anthoney, Chris Twelves, Debbie Beirne, Poulam Patel, Dearbhaile Odonnell, Suzanne Watt, Michael Waller, Allan Dietz, Philip RobinsonAlan Melcher

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Dendritic cells (DC) are under intense preclinical and early clinical evaluation for the immunotherapy of cancer. However, the optimal culture conditions and route of delivery for DC vaccination have not been established. Here we describe the first human application of DC matured with the bacterial agent OK432 (OK-DC), using a short-term serum-free culture protocol, which generates mature DC from CD14 precursors after 5 days. These cells were prepared within the framework of a National Blood Service facility, demonstrating that DC represent a product which is potentially deliverable alongside current standardized cell therapies within the UK National Health Service. In vitro analysis confirmed that OK-DC were mature, secreted tumor necrosis factor-α, interleukin-6, and interleukin-12, and stimulated both T cell and natural killer cell function. To explore effective delivery of OK-DC to lymph nodes, we performed an initial clinical tracking study of radioactively labeled, unpulsed OK-DC after intralymphatic injection into the dorsum of the foot. We showed that injected DC rapidly localized to ipsilateral pelvic lymph nodes, but did not disseminate to more distant nodes over a 48-hour period. There was no significant toxicity associated with OK-DC delivery. These results show that OK-DC are suitable for clinical use, and that intralymphatic delivery is feasible for localizing cells to sites where optimal priming of innate and adaptive antitumor immunity is likely to occur.

Original languageEnglish (US)
Pages (from-to)66-78
Number of pages13
JournalJournal of Immunotherapy
Volume32
Issue number1
DOIs
StatePublished - Jan 1 2009

Keywords

  • Dendritic cells
  • Intralymphatic delivery
  • NK cells
  • OK432
  • T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

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  • Cite this

    West, E., Morgan, R., Scott, K., Merrick, A., Lubenko, A., Pawson, D., Selby, P., Hatfield, P., Prestwich, R., Fraser, S., Eves, D., Anthoney, A., Twelves, C., Beirne, D., Patel, P., Odonnell, D., Watt, S., Waller, M., Dietz, A., ... Melcher, A. (2009). Clinical grade OK432-activated dendritic cells: In vitro characterization and tracking during intralymphatic delivery. Journal of Immunotherapy, 32(1), 66-78. https://doi.org/10.1097/CJI.0b013e31818be071