Aptamer-targeted antigen delivery

Brian C. Wengerter, Joseph A. Katakowski, Jacob M. Rosenberg, Chae Gyu Park, Steven C. Almo, Deborah Palliser, Matthew Levy

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Effective therapeutic vaccines often require activation of T cell-mediated immunity. Robust T cell activation, including CD8 T cell responses, can be achieved using antibodies or antibody fragments to direct antigens of interest to professional antigen presenting cells. This approach represents an important advance in enhancing vaccine efficacy. Nucleic acid aptamers present a promising alternative to protein-based targeting approaches. We have selected aptamers that specifically bind the murine receptor, DEC205, a C-type lectin expressed predominantly on the surface of CD8α + dendritic cells (DCs) that has been shown to be efficient at facilitating antigen crosspresentation and subsequent CD8 + T cell activation. Using a minimized aptamer conjugated to the model antigen ovalbumin (OVA), DEC205-targeted antigen crosspresentation was verified in vitro and in vivo by proliferation and cytokine production by primary murine CD8 + T cells expressing a T cell receptor specific for the major histocompatibility complex (MHC) I-restricted OVA 257-264 peptide SIINFEKL. Compared with a nonspecific ribonucleic acid (RNA) of similar length, DEC205 aptamer-OVA-mediated antigen delivery stimulated strong proliferation and production of interferon (IFN)-γ and interleukin (IL)-2. The immune responses elicited by aptamer-OVA conjugates were sufficient to inhibit the growth of established OVA-expressing B16 tumor cells. Our results demonstrate a new application of aptamer technology for the development of effective T cell-mediated vaccines.

Original languageEnglish (US)
Pages (from-to)1375-1387
Number of pages13
JournalMolecular Therapy
Volume22
Issue number7
DOIs
StatePublished - Jul 2014

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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    Wengerter, B. C., Katakowski, J. A., Rosenberg, J. M., Park, C. G., Almo, S. C., Palliser, D., & Levy, M. (2014). Aptamer-targeted antigen delivery. Molecular Therapy, 22(7), 1375-1387. https://doi.org/10.1038/mt.2014.51