Presentation of tumor antigens by dendritic cells genetically modified with viral and nonviral vectors

Michal Lotem, Yangbing Zhao, John Riley, Patrick Hwu, Richard A. Morgan, Steven A. Rosenberg, Maria R. Parkhurst

Research output: Contribution to journalArticle

Abstract

Genetic modification of dendritic cells (DCs) with recombinant vectors encoding tumor antigens may aid in developing new immunotherapeutic treatments for patients with cancer. Here, we characterized antigen presentation by human DCs genetically modified with plasmid cDNAs, RNAs, adenoviruses, or retroviruses, encoding the melanoma antigen gp100 or the tumor-testis antigen NY-ESO-1. Monocyte-derived DCs were electroporated with cDNAs or RNAs, or transduced with adenoviruses. CD34 hematopoietic stem cell-derived DCs were used for retroviral transduction. Genetically modified DCs were coincubated with CD8 and CD4 T cells that recognized major histocompatibility complex class I- and class II-restricted epitopes from gp100 and NY-ESO-1, and specific recognition was evaluated by interferonγ secretion. Cytokine release by both CD8 and CD4 T cells was consistently higher in response to DCs modified with adenoviruses than cDNAs or RNAs, and maturation of DCs after genetic modification did not consistently alter patterns of recognition. Also, retrovirally transduced DCs encoding gp100 were well recognized by both CD8 and CD4 T cells. These data suggest that DCs transduced with viral vectors may be more efficient than DCs transfected with cDNAs or RNAs for the induction of tumor reactive CD8 and CD4 T cells in vitro and in human vaccination trials.

Original languageEnglish (US)
Pages (from-to)616-627
Number of pages12
JournalJournal of Immunotherapy
Volume29
Issue number6
DOIs
StatePublished - Nov 2006

Keywords

  • Adenovirus
  • Dendritic cells
  • Electroporation
  • Nonviral vectors
  • Retrovirus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

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  • Cite this

    Lotem, M., Zhao, Y., Riley, J., Hwu, P., Morgan, R. A., Rosenberg, S. A., & Parkhurst, M. R. (2006). Presentation of tumor antigens by dendritic cells genetically modified with viral and nonviral vectors. Journal of Immunotherapy, 29(6), 616-627. https://doi.org/10.1097/01.cji.0000211312.36363.56