Peptide-conjugated PAMAM dendrimer as a universal DNA vaccine platform to target antigen-presenting cells

Pirouz Daftarian, Angel E. Kaifer, Wei Li, Bonnie B. Blomberg, Daniela Frasca, Felix Roth, Raquibul Chowdhury, Eric A. Berg, Jordan B. Fishman, Husain A. Al Sayegh, Pat Blackwelder, Luca Inverardi, Victor L. Perez, Vance Lemmon, Paolo Serafini

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63 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)7452-7462
Number of pages11
JournalCancer Research
Volume71
Issue number24
DOIs
StatePublished - Dec 15 2011

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Daftarian, P., Kaifer, A. E., Li, W., Blomberg, B. B., Frasca, D., Roth, F., Chowdhury, R., Berg, E. A., Fishman, J. B., Al Sayegh, H. A., Blackwelder, P., Inverardi, L., Perez, V. L., Lemmon, V., & Serafini, P. (2011). Peptide-conjugated PAMAM dendrimer as a universal DNA vaccine platform to target antigen-presenting cells. Cancer Research, 71(24), 7452-7462. https://doi.org/10.1158/0008-5472.CAN-11-1766