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Peptide-Conjugated PAMAM Dendrimer as a Universal DNA Vaccine Platform to Target Antigen-Presenting Cells
Cancer Research
  • Pirouz M. Daftarian, University of Miami
  • Angel E. Kaifer, University of Miami
  • Wei Li, University of Miami
  • Bonnie B. Blomberg, University of Miami
  • Daniela Frasca, University of Miami
  • Felix Roth, University of Miami
  • Raquibul Chowdhury, University of Miami
  • Husain Ala Al Sayegh, University of Miami
  • Patricia Blackwelder, University of Miami
  • Luca Inverardi, University of Miami
  • Victor L. Perez, University of Miami
  • Vance Lemmon, University of Miami
  • Paolo Serafini, University of Miami
Document Type
Article
Publication Date
12-15-2011
Peer Reviewed
1
Abstract
DNA-based vaccines hold promise to outperform conventional antigen-based vaccines by virtue of many unique features. However, DNA vaccines have thus far fallen short of expectations, due in part to poor targeting of professional antigen-presenting cells (APC) and low immunogenicity. In this study, we describe a new platform for effective and selective delivery of DNA to APCs in vivo that offers intrinsic immune-enhancing characteristics. This platform is based on conjugation of fifth generation polyamidoamine (G5-PAMAM) dendrimers, a DNA-loading surface, with MHC class II–targeting peptides that can selectively deliver these dendrimers to APCs under conditions that enhance their immune stimulatory potency. DNA conjugated with this platform efficiently transfected murine and human APCs in vitro. Subcutaneous administration of DNA-peptide-dendrimer complexes in vivo preferentially transfected dendritic cells (DC) in the draining lymph nodes, promoted generation of high affinity T cells, and elicited rejection of established tumors. Taken together, our findings show how PAMAM dendrimer complexes can be used for high transfection efficiency and effective targeting of APCs in vivo, conferring properties essential to generate effective DNA vaccines.
Comments

©2011 American Association for Cancer Research.

Additional Comments
This work was support by the Sylvester Cancer Center, the Coulter Center, and the Susan Komen for the cure foundation award number KG090350.
DOI
10.1158/0008-5472.CAN-11-1766
Citation Information
Pirouz M. Daftarian, Angel E. Kaifer, Wei Li, Bonnie B. Blomberg, et al.. "Peptide-Conjugated PAMAM Dendrimer as a Universal DNA Vaccine Platform to Target Antigen-Presenting Cells" Cancer Research Vol. 71 Iss. 24 (2011) p. 7452 - 7462 ISSN: 0008-5472
Available at: http://works.bepress.com/patricia-blackwelder/26/