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Reprogramming tumor-associated dendritic cells in vivo using miRNA mimetics triggers protective immunity against ovarian cancer.

Publication ,  Journal Article
Cubillos-Ruiz, JR; Baird, JR; Tesone, AJ; Rutkowski, MR; Scarlett, UK; Camposeco-Jacobs, AL; Anadon-Arnillas, J; Harwood, NM; Korc, M ...
Published in: Cancer Res
April 1, 2012

Modulating the activity of miRNAs provides opportunities for novel cancer interventions. However, low bioavailability and poor cellular uptake are major challenges for delivering miRNA mimetics specifically to tumor cells. Here, we took advantage of the spontaneous enhanced endocytic activity of ovarian cancer-associated dendritic cells (DC) to selectively supplement the immunostimulatory miRNA miR-155. In vivo processing of nanoparticles carrying oligonucleotide duplexes mimicking the bulged structure of endogenous pre-miRNA (but not siRNA-like oligonucleotides) dramatically augmented miR-155 activity without saturating the RNA-induced silencing complex. Endogenous processing of synthetic miR-155 favored Ago2 and, to a lesser extent, Ago4 loading, resulting in genome-wide transcriptional changes that included silencing of multiple immunosuppressive mediators. Correspondingly, tumor-infiltrating DCs were transformed from immunosuppressive to highly immunostimulatory cells capable of triggering potent antitumor responses that abrogated the progression of established ovarian cancers. Our results show both the feasibility and therapeutic potential of supplementing/replenishing miRNAs in vivo using nonviral approaches to boost protective immunity against lethal tumors. Thus, we provide a platform, an optimized design, and a mechanistic rationale for the clinical testing of nonviral miRNA mimetics.

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Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

April 1, 2012

Volume

72

Issue

7

Start / End Page

1683 / 1693

Location

United States

Related Subject Headings

  • Tumor Microenvironment
  • Transcriptome
  • RNA-Induced Silencing Complex
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • MicroRNAs
  • Mice, Inbred C57BL
  • Mice
  • Humans
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
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Cubillos-Ruiz, J. R., Baird, J. R., Tesone, A. J., Rutkowski, M. R., Scarlett, U. K., Camposeco-Jacobs, A. L., … Conejo-Garcia, J. R. (2012). Reprogramming tumor-associated dendritic cells in vivo using miRNA mimetics triggers protective immunity against ovarian cancer. Cancer Res, 72(7), 1683–1693. https://doi.org/10.1158/0008-5472.CAN-11-3160
Cubillos-Ruiz, Juan R., Jason R. Baird, Amelia J. Tesone, Melanie R. Rutkowski, Uciane K. Scarlett, Ana L. Camposeco-Jacobs, Jorge Anadon-Arnillas, et al. “Reprogramming tumor-associated dendritic cells in vivo using miRNA mimetics triggers protective immunity against ovarian cancer.Cancer Res 72, no. 7 (April 1, 2012): 1683–93. https://doi.org/10.1158/0008-5472.CAN-11-3160.
Cubillos-Ruiz JR, Baird JR, Tesone AJ, Rutkowski MR, Scarlett UK, Camposeco-Jacobs AL, et al. Reprogramming tumor-associated dendritic cells in vivo using miRNA mimetics triggers protective immunity against ovarian cancer. Cancer Res. 2012 Apr 1;72(7):1683–93.
Cubillos-Ruiz, Juan R., et al. “Reprogramming tumor-associated dendritic cells in vivo using miRNA mimetics triggers protective immunity against ovarian cancer.Cancer Res, vol. 72, no. 7, Apr. 2012, pp. 1683–93. Pubmed, doi:10.1158/0008-5472.CAN-11-3160.
Cubillos-Ruiz JR, Baird JR, Tesone AJ, Rutkowski MR, Scarlett UK, Camposeco-Jacobs AL, Anadon-Arnillas J, Harwood NM, Korc M, Fiering SN, Sempere LF, Conejo-Garcia JR. Reprogramming tumor-associated dendritic cells in vivo using miRNA mimetics triggers protective immunity against ovarian cancer. Cancer Res. 2012 Apr 1;72(7):1683–1693.

Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

April 1, 2012

Volume

72

Issue

7

Start / End Page

1683 / 1693

Location

United States

Related Subject Headings

  • Tumor Microenvironment
  • Transcriptome
  • RNA-Induced Silencing Complex
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • MicroRNAs
  • Mice, Inbred C57BL
  • Mice
  • Humans
  • Female