title: Aptamer-targeted antigen delivery.
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 OVA257-264 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.
authors.affiliation: Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Wengerter
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Katakowski
authors.affiliation: Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, New York, USA; Current address: Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Rosenberg
authors.affiliation: Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, New York, USA; Current address: Laboratory of Immunology, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Chae Gyu
authors.initials: CG
authors.lastname: Park
authors.affiliation: Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Almo
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA. Electronic address: deborah.palliser@einstein.yu.edu.
authors.forename: Deborah
authors.initials: D
authors.lastname: Palliser
authors.affiliation: Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York, USA. Electronic address: matthew.levy@einstein.yu.edu.
authors.forename: Matthew
authors.initials: M
authors.lastname: Levy
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology*; D052157:Aptamers, Nucleotide / Q000008:administration & dosage* / Q000235:genetics*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D003713:Dendritic Cells / Q000378:metabolism; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D000941:Antigens; D052157:Aptamers, Nucleotide; D007371:Interferon-gamma