Peptide-Conjugated PAMAM Dendrimer as a Universal DNA Vaccine Platform to Target Antigen-Presenting Cells

Authors

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
21st Century Biochemicals, Inc.
Husain Ala Al Sayegh, University of MiamiFollow
Patricia Blackwelder, University of MiamiFollow
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 Title

Cancer Research

ISSN

0008-5472

Publication Date

12-15-2011

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.

DOI

10.1158/0008-5472.CAN-11-1766

Volume

71

Issue

24

First Page

7452

Last Page

7462

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.

NSUWorks Citation

Pirouz M. Daftarian; Angel E. Kaifer; Wei Li; Bonnie B. Blomberg; Daniela Frasca; Felix Roth; Raquibul Chowdhury; 21st Century Biochemicals, Inc.; Husain Ala Al Sayegh; Patricia Blackwelder; Luca Inverardi; Victor L. Perez; Vance Lemmon; and Paolo Serafini. 2011. Peptide-Conjugated PAMAM Dendrimer as a Universal DNA Vaccine Platform to Target Antigen-Presenting Cells .Cancer Research , (24) : 7452 -7462. https://nsuworks.nova.edu/occ_facarticles/444.