Single-walled carbon nanotubes deliver peptide antigen into dendritic cells and enhance IgG responses to tumor-associated antigens Journal Article

   


Authors: Villa, C. H.; Dao, T.; Ahearn, I.; Fehrenbacher, N.; Casey, E.; Rey, D. A.; Korontsvit, T.; Zakhaleva, V.; Batt, C. A.; Philips, M. R.; Scheinberg, D. A.
Article 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. © 2011 American Chemical Society.
Keywords: clinical trial; tumor antigen; immunology; dendritic cells; immune response; antigens; tumors; antibody response; peptides; medical nanotechnology; in-vivo; nanomedicine; binding affinities; binding energy; mammals; in-vitro; cells; molecules; t-cell response; dose-dependent manner; carbon nanotubes; wilms' tumor antigen; peptide vaccines; antigen presenting cells; balb/c mice; class ii; human tumor antigens; humoral immune response; immunogens; mouse cells; nanomedicines; peptide ligand; single-wall carbon nanotubes; single-walled carbon nanotubes (swcn)
Journal Title: ACS Nano
Volume: 5
Issue: 7
ISSN: 1936-0851
Publisher: American Chemical Society  
Date Published: 2011-07-26
Start Page: 5300
End Page: 5311
Language: English
DOI: 10.1021/nn200182x
PROVIDER: scopus
PMCID: PMC3143710
PUBMED: 21682329
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-79961033075&partnerID=40&md5=b9501ebeffb9ad8c500919b48adf7710
Notes: --- - "Export Date: 3 October 2011" - "Source: Scopus"
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MSK Authors
  1. David Scheinberg
    499 Scheinberg
  2. Tao Dao
    81 Dao
  3. Emily Catherine Casey
    9 Casey
  4. Carlos H Villa
    13 Villa
  5. Viktoriya Zakhaleva
    29 Zakhaleva
  6. Tatyana Korontsvit
    53 Korontsvit
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