Contact-activated monocytes: Efficient antigen presenting cells for the stimulation of antigen-specific T cells

Ann Leen, Maheshika Ratnayake, Aaron Foster, Kenneth Heym, Nabil Ahmed, Cliona M. Rooney, Stephen Gottschalk

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Mature dendritic cells (DCs) are potent antigen presenting cells (APCs) that have been used in vaccine studies and adoptive immunotherapy protocols. For many clinical studies DCs are derived from monocytes in the presence of cytokines, which are expensive and often unavailable for clinical use. Here we describe a cytokine independent method for the differentiation of monocytes into APCs for the reactivation of antigen-specific memory T cells from both healthy donors and cancer patients. Contact activation of monocytes resulted in secretion of proinflammatory cytokines, such as IL-8, and increased cell surface expression of costimulatory molecules. To determine if activated monocytes (actMo) like DC can reactivate antigen-specific CTL, they were transduced with adenoviral vectors encoding the subdominant Epstein Barr virus antigens, latent membrane proteins (LMP) 1 and 2, which are expressed in Epstein Barr virus-positive malignancies. Stimulation of peripheral blood mononuclear cells with LMP1- and LMP2-expressing actMo activated LMP1- and LMP2-specific T cells, which could be further expanded with LMP1 or LMP2 expressing lymphoblastoid cell lines. The use of actMo as APCs simplifies the production/manufacture of antigen-specific T cells for clinical trials.

Original languageEnglish (US)
Pages (from-to)96-107
Number of pages12
JournalJournal of Immunotherapy
Volume30
Issue number1
DOIs
StatePublished - Jan 2007

Keywords

  • Adoptive immunotherapy
  • Antigen-specific T cells
  • Dendritic cells
  • Epstein Barr virus
  • Monocytes

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Immunology

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