Cancer Therapy: Clinical Targeting of In-Labeled Dendritic Cell Human Vaccines Improved by Reducing Number of Cells

نویسندگان

  • Erik H.J.G. Aarntzen
  • Mangala Srinivas
  • Fernando Bonetto
  • Luis J. Cruz
  • Pauline Verdijk
  • Gerty Schreibelt
  • Mandy van de Rakt
  • W. Joost Lesterhuis
  • Maichel van Riel
  • Cornelius J.A. Punt
  • Gosse J. Adema
  • Arend Heerschap
  • Carl G. Figdor
  • Wim J. Oyen
  • Jolanda M. de Vries
چکیده

Purpose: Anticancer dendritic cell (DC) vaccines require the DCs to relocate to lymph nodes (LN) to trigger immune responses.However, thesemigration rates are typically very poor. Improving the targeting of ex vivo generatedDCs to LNsmight increase vaccine efficacy and reduce costs.We investigatedDCmigration in vivo in humans under different conditions. Experimental Design:HLA-A 02:01 patients with melanoma were vaccinated with mature DCs loaded with tyrosinase and gp100 peptides together with keyhole limpet hemocyanin (NCT00243594). For this study, patients received an additional intradermal vaccinationwith In-labeledmatureDCs. The injection site was pretreated with nonloaded, activated DCs, TNFa, or Imiquimod; granulocyte macrophage colonystimulating factor was coinjected or smaller numbers of DCs were injected. Migration was measured by scintigraphy and comparedwith an intrapatient control vaccination. In an ex vivo tissuemodel, wemeasured CCL21-directed migration of F-labeled DCs over a period of up to 12 hours using F MRI to supplement

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تاریخ انتشار 2013