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

Pirouz Daftarian, Angel 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 A Inverardi, Victor L Perez Quinones, Vance Lemmon, Paolo Serafini

Research output: Contribution to journalArticle

54 Citations (Scopus)

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

Fingerprint

DNA Vaccines
Antigen-Presenting Cells
Dendrimers
Peptides
DNA
Dendritic Cells
Transfection
Vaccines
Lymph Nodes
T-Lymphocytes
Antigens
PAMAM Starburst
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Peptide-conjugated PAMAM dendrimer as a universal DNA vaccine platform to target antigen-presenting cells. / Daftarian, Pirouz; Kaifer, Angel; Li, Wei; Blomberg, Bonnie B; Frasca, Daniela; Roth, Felix; Chowdhury, Raquibul; Berg, Eric A.; Fishman, Jordan B.; Al Sayegh, Husain A.; Blackwelder, Pat; Inverardi, Luca A; Perez Quinones, Victor L; Lemmon, Vance; Serafini, Paolo.

In: Cancer Research, Vol. 71, No. 24, 15.12.2011, p. 7452-7462.

Research output: Contribution to journalArticle

Daftarian, P, Kaifer, A, Li, W, Blomberg, BB, Frasca, D, Roth, F, Chowdhury, R, Berg, EA, Fishman, JB, Al Sayegh, HA, Blackwelder, P, Inverardi, LA, Perez Quinones, VL, Lemmon, V & Serafini, P 2011, 'Peptide-conjugated PAMAM dendrimer as a universal DNA vaccine platform to target antigen-presenting cells', Cancer Research, vol. 71, no. 24, pp. 7452-7462. https://doi.org/10.1158/0008-5472.CAN-11-1766
Daftarian, Pirouz ; Kaifer, Angel ; Li, Wei ; Blomberg, Bonnie B ; Frasca, Daniela ; Roth, Felix ; Chowdhury, Raquibul ; Berg, Eric A. ; Fishman, Jordan B. ; Al Sayegh, Husain A. ; Blackwelder, Pat ; Inverardi, Luca A ; Perez Quinones, Victor L ; Lemmon, Vance ; Serafini, Paolo. / Peptide-conjugated PAMAM dendrimer as a universal DNA vaccine platform to target antigen-presenting cells. In: Cancer Research. 2011 ; Vol. 71, No. 24. pp. 7452-7462.
@article{599f853389a547ab822793bba2f15e43,
title = "Peptide-conjugated PAMAM dendrimer as a universal DNA vaccine platform to target antigen-presenting cells",
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.",
author = "Pirouz Daftarian and Angel Kaifer and Wei Li and Blomberg, {Bonnie B} and Daniela Frasca and Felix Roth and Raquibul Chowdhury and Berg, {Eric A.} and Fishman, {Jordan B.} and {Al Sayegh}, {Husain A.} and Pat Blackwelder and Inverardi, {Luca A} and {Perez Quinones}, {Victor L} and Vance Lemmon and Paolo Serafini",
year = "2011",
month = "12",
day = "15",
doi = "10.1158/0008-5472.CAN-11-1766",
language = "English",
volume = "71",
pages = "7452--7462",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "24",

}

TY - JOUR

T1 - Peptide-conjugated PAMAM dendrimer as a universal DNA vaccine platform to target antigen-presenting cells

AU - Daftarian, Pirouz

AU - Kaifer, Angel

AU - Li, Wei

AU - Blomberg, Bonnie B

AU - Frasca, Daniela

AU - Roth, Felix

AU - Chowdhury, Raquibul

AU - Berg, Eric A.

AU - Fishman, Jordan B.

AU - Al Sayegh, Husain A.

AU - Blackwelder, Pat

AU - Inverardi, Luca A

AU - Perez Quinones, Victor L

AU - Lemmon, Vance

AU - Serafini, Paolo

PY - 2011/12/15

Y1 - 2011/12/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84255170451&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84255170451&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-11-1766

DO - 10.1158/0008-5472.CAN-11-1766

M3 - Article

VL - 71

SP - 7452

EP - 7462

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 24

ER -