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Synthetic double-stranded RNA poly(I:C) as a potent peptide vaccine adjuvant: therapeutic activity against human cervical cancer in a rodent model

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Abstract

Due to the inherent lack of immunogenicity of peptides, it is generally recognized that the strong inflammatory signals that are required to elicit specific responses against peptide-based therapeutic tumor vaccines may not be provided by the standard/conventional vaccine adjuvants. In this study, we have demonstrated dsRNA in the form of synthetic pI:C as a potent adjuvant to enhance the specific anti-tumor immune responses against a peptide-based vaccine. When complexed with an MHC I-restricted minimal peptide epitope derived from the HPV 16 E7 protein, the resulting pI:C/E749–57 molecular complex induced strong E749–57-specific CTL responses that caused significant regressions of model human cervical cancer tumors pre-established in mice. In addition, although the proportion of DCs in tumor-bearing mice was significantly decreased when compared to that in naïve mice, immunization with pI:C/E749–57 restored the proportion of DCs in tumor-bearing mice. Double-stranded RNA may hold a great potential as an adjuvant to induce cellular immune responses for tumor immunotherapy.

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Abbreviations

CTL:

Cytotoxic T lymphocyte

DC:

Dendritic cells

LN:

Lymph node

HPV:

Human papillomavirus

TLR:

Toll-like receptor

PAMP:

Pathogen-associated molecular pattern

MHC:

Major histocompatibility complex

pDC:

Plasmocytoid DC

mDC:

Myeloid DC

NK:

Natural killer

pI:C or Poly(I:C):

Polyinosine-polycytidylic acid

CFSE:

5-(and-6-)-carboxylfluorescein diacetate, succinimidayl ester

s.c.:

Subcutaneous

HLA:

Human lymphocyte antigen

IFN:

Interferon

TAA:

Tumor-associated antigens

TSA:

Tumor-specific antigens

IFA:

Incomplete Freund’s adjuvant

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Acknowledgement

Flow cytometry analyses were completed in the Flow Cytometry and Cell Sorting Facilities in the Environmental Health Science Center at the Oregon State University.

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  1. Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR, 97331, USA

    Zhengrong Cui & Fu Qiu

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  1. Zhengrong Cui
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Correspondence to Zhengrong Cui.

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Cui, Z., Qiu, F. Synthetic double-stranded RNA poly(I:C) as a potent peptide vaccine adjuvant: therapeutic activity against human cervical cancer in a rodent model. Cancer Immunol Immunother 55, 1267–1279 (2006). https://doi.org/10.1007/s00262-005-0114-6

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