title: Single-walled carbon nanotubes deliver peptide antigen into dendritic cells and enhance IgG responses to tumor-associated antigens.
abstract: We studied the feasibility of using single-wall carbon nanotubes (SWNTs) as antigen carriers to improve immune responses to peptides that are weak immunogens, a characteristic typical of human tumor antigens. Binding and presentation of peptide antigens by the MHC molecules of antigen presenting cells (APCs) is essential to mounting an effective immune response. The Wilm's tumor protein (WT1) is upregulated in many human leukemias and cancers and several vaccines directed at this protein are in human clinical trials. WT1 peptide 427 induces human CD4 T cell responses in the context of multiple human HLA-DR.B1 molecules, but the peptide has a poor binding affinity to BALB/c mouse MHC class II molecules. We used novel, spectrally quantifiable chemical approaches to covalently append large numbers of peptide ligands (0.4 mmol/g) onto solubilized SWNT scaffolds. Peptide-SWNT constructs were rapidly internalized into professional APCs (dendritic cells and macrophages) within minutes in vitro, in a dose dependent manner. Immunization of BALB/c mice with the SWNT-peptide constructs mixed with immunological adjuvant induced specific IgG responses against the peptide, while the peptide alone or peptide mixed with the adjuvant did not induce such a response. The conjugation of the peptide to SWNT did not enhance the peptide-specific CD4 T cell response in human and mouse cells, in vitro. The solubilized SWNTs alone were nontoxic in vitro, and we did not detect antibody responses to SWNT in vivo. These results demonstrated that SWNTs are able to serve as antigen carriers for delivery into APCs to induce humoral immune responses against weak tumor antigens.
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA.
authors.forename: Carlos H
authors.initials: CH
authors.lastname: Villa
authors.forename: Tao
authors.initials: T
authors.lastname: Dao
authors.forename: Ian
authors.initials: I
authors.lastname: Ahearn
authors.forename: Nicole
authors.initials: N
authors.lastname: Fehrenbacher
authors.forename: Emily
authors.initials: E
authors.lastname: Casey
authors.forename: Diego A
authors.initials: DA
authors.lastname: Rey
authors.forename: Tatyana
authors.initials: T
authors.lastname: Korontsvit
authors.forename: Victoriya
authors.initials: V
authors.lastname: Zakhaleva
authors.forename: Carl A
authors.initials: CA
authors.lastname: Batt
authors.forename: Mark R
authors.initials: MR
authors.lastname: Philips
authors.forename: David A
authors.initials: DA
authors.lastname: Scheinberg
mesh_terms: D000447:Aldehydes / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism*; D001391:Azo Compounds / Q000737:chemistry; D001692:Biological Transport; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D019855:Ethylene Glycol / Q000737:chemistry; D005260:Female; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007074:Immunoglobulin G / Q000276:immunology*; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D037742:Nanotubes, Carbon / Q000737:chemistry* / Q000633:toxicity; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D013882:Thiosemicarbazones / Q000737:chemistry; D025721:WT1 Proteins / Q000737:chemistry
chemical_list: D000447:Aldehydes; D000951:Antigens, Neoplasm; D001391:Azo Compounds; D004337:Drug Carriers; D007074:Immunoglobulin G; D037742:Nanotubes, Carbon; D010446:Peptide Fragments; D013882:Thiosemicarbazones; D025721:WT1 Proteins; C512188:azomethine; D019855:Ethylene Glycol