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Systemic activation of antigen-presenting cells via RNA-loaded nanoparticles.

Publication ,  Journal Article
Sayour, EJ; De Leon, G; Pham, C; Grippin, A; Kemeny, H; Chua, J; Huang, J; Sampson, JH; Sanchez-Perez, L; Flores, C; Mitchell, DA
Published in: Oncoimmunology
2017

While RNA-pulsed dendritic cell (DC) vaccines have shown promise, the advancement of cellular therapeutics is fraught with developmental challenges. To circumvent the challenges of cellular immunotherapeutics, we developed clinically translatable nanoliposomes that can be combined with tumor-derived RNA to generate personalized tumor RNA-nanoparticles (NPs) with considerable scale-up capacity. RNA-NPs bypass MHC restriction, are amenable to central distribution, and can provide near immediate immune induction. We screened commercially available nanoliposomal preparations and identified the cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) as an efficient mRNA courier to antigen-presenting cells (APCs). When administered intravenously, RNA-NPs mediate systemic activation of APCs in reticuloendothelial organs such as the spleen, liver, and bone marrow. RNA-NPs increase percent expression of MHC class I/II, B7 co-stimulatory molecules, and maturation markers on APCs (all vital for T-cell activation). RNA-NPs also increase activation markers on tumor APCs and elicit potent expansion of antigen-specific T-cells superior to peptide vaccines formulated in complete Freund's adjuvant. We demonstrate that both model antigen-encoding and physiologically-relevant tumor-derived RNA-NPs expand potent antitumor T-cell immunity. RNA-NPs were shown to induce antitumor efficacy in a vaccine model and functioned as a suitable alternative to DCs in a stringent cellular immunotherapy model for a radiation/temozolomide resistant invasive murine high-grade glioma. Although cancer vaccines have suffered from weak immunogenicity, we have advanced a RNA-NP formulation that systemically activates host APCs precipitating activated T-cell frequencies necessary to engender antitumor efficacy. RNA-NPs can thus be harnessed as a more feasible and effective immunotherapy to re-program host-immunity.

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Published In

Oncoimmunology

DOI

ISSN

2162-4011

Publication Date

2017

Volume

6

Issue

1

Start / End Page

e1256527

Location

United States

Related Subject Headings

  • 3211 Oncology and carcinogenesis
  • 3204 Immunology
  • 1112 Oncology and Carcinogenesis
  • 1107 Immunology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Sayour, E. J., De Leon, G., Pham, C., Grippin, A., Kemeny, H., Chua, J., … Mitchell, D. A. (2017). Systemic activation of antigen-presenting cells via RNA-loaded nanoparticles. Oncoimmunology, 6(1), e1256527. https://doi.org/10.1080/2162402X.2016.1256527
Sayour, Elias J., Gabriel De Leon, Christina Pham, Adam Grippin, Hanna Kemeny, Joshua Chua, Jianping Huang, et al. “Systemic activation of antigen-presenting cells via RNA-loaded nanoparticles.Oncoimmunology 6, no. 1 (2017): e1256527. https://doi.org/10.1080/2162402X.2016.1256527.
Sayour EJ, De Leon G, Pham C, Grippin A, Kemeny H, Chua J, et al. Systemic activation of antigen-presenting cells via RNA-loaded nanoparticles. Oncoimmunology. 2017;6(1):e1256527.
Sayour, Elias J., et al. “Systemic activation of antigen-presenting cells via RNA-loaded nanoparticles.Oncoimmunology, vol. 6, no. 1, 2017, p. e1256527. Pubmed, doi:10.1080/2162402X.2016.1256527.
Sayour EJ, De Leon G, Pham C, Grippin A, Kemeny H, Chua J, Huang J, Sampson JH, Sanchez-Perez L, Flores C, Mitchell DA. Systemic activation of antigen-presenting cells via RNA-loaded nanoparticles. Oncoimmunology. 2017;6(1):e1256527.

Published In

Oncoimmunology

DOI

ISSN

2162-4011

Publication Date

2017

Volume

6

Issue

1

Start / End Page

e1256527

Location

United States

Related Subject Headings

  • 3211 Oncology and carcinogenesis
  • 3204 Immunology
  • 1112 Oncology and Carcinogenesis
  • 1107 Immunology