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Paired Toll-like receptor agonists enhance vaccine therapy through induction of interleukin-12.

Publication ,  Journal Article
Zheng, R; Cohen, PA; Paustian, CA; Johnson, TD; Lee, WT; Shu, S; Koski, GK
Published in: Cancer research
June 2008

Minimal requirements for generating effective immunity include the delivery of antigenic (signal 1) and costimulatory (signal 2) signals to T lymphocytes. Recently, a class of third signals, often delivered by antigen-presenting dendritic cells, has been shown to greatly enhance immune responses, especially against tumors. Among signal 3 factors, interleukin (IL)-12 is particularly effective and can be conditionally induced by agonists of Toll-like transmembrane receptors (TLR). In this study, we assessed the therapeutic effect of adjuvant TLR agonist administration upon the capacity of dendritic cell (DC)-tumor electrofusion hybrids to eradicate established MCA205 sarcomas in syngeneic mice. Paired, but not solitary combinations of polyinosine:polycytadilic acid (P[I:C]; TLR3 agonist) and CpG DNA (ODN1826l; TLR9 agonist) stimulated IL-12 secretion from DCs in vitro and synergized with vaccination to achieve potent tumor rejection. Therapeutic effects, however, required coadministration of paired TLR agonists and DC-tumor fusion hybrids. The administration of TLR agonists alone or with fusion vaccine induced transient splenomegaly but without apparent toxicity. The therapeutic effects of this immunization regimen were significantly abrogated through the neutralization of IL-12p70, indicating that production of this third signal was essential to the observed tumor regression. These results show the profound functional consequences of TLR cooperativity and further highlight the critical role of IL-12 in antitumor immunity.

Duke Scholars

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Published In

Cancer research

DOI

EISSN

1538-7445

ISSN

0008-5472

Publication Date

June 2008

Volume

68

Issue

11

Start / End Page

4045 / 4049

Related Subject Headings

  • Vaccines
  • Toll-Like Receptors
  • Oncology & Carcinogenesis
  • Mice, Inbred C57BL
  • Mice
  • Interleukin-12
  • Female
  • Enzyme-Linked Immunosorbent Assay
  • Cell Separation
  • Cancer Vaccines
 

Citation

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Zheng, R., Cohen, P. A., Paustian, C. A., Johnson, T. D., Lee, W. T., Shu, S., & Koski, G. K. (2008). Paired Toll-like receptor agonists enhance vaccine therapy through induction of interleukin-12. Cancer Research, 68(11), 4045–4049. https://doi.org/10.1158/0008-5472.can-07-6669
Zheng, Rongxiu, Peter A. Cohen, Christopher A. Paustian, Terrence D. Johnson, Walter T. Lee, Suyu Shu, and Gary K. Koski. “Paired Toll-like receptor agonists enhance vaccine therapy through induction of interleukin-12.Cancer Research 68, no. 11 (June 2008): 4045–49. https://doi.org/10.1158/0008-5472.can-07-6669.
Zheng R, Cohen PA, Paustian CA, Johnson TD, Lee WT, Shu S, et al. Paired Toll-like receptor agonists enhance vaccine therapy through induction of interleukin-12. Cancer research. 2008 Jun;68(11):4045–9.
Zheng, Rongxiu, et al. “Paired Toll-like receptor agonists enhance vaccine therapy through induction of interleukin-12.Cancer Research, vol. 68, no. 11, June 2008, pp. 4045–49. Epmc, doi:10.1158/0008-5472.can-07-6669.
Zheng R, Cohen PA, Paustian CA, Johnson TD, Lee WT, Shu S, Koski GK. Paired Toll-like receptor agonists enhance vaccine therapy through induction of interleukin-12. Cancer research. 2008 Jun;68(11):4045–4049.

Published In

Cancer research

DOI

EISSN

1538-7445

ISSN

0008-5472

Publication Date

June 2008

Volume

68

Issue

11

Start / End Page

4045 / 4049

Related Subject Headings

  • Vaccines
  • Toll-Like Receptors
  • Oncology & Carcinogenesis
  • Mice, Inbred C57BL
  • Mice
  • Interleukin-12
  • Female
  • Enzyme-Linked Immunosorbent Assay
  • Cell Separation
  • Cancer Vaccines