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Adjuvants targeting innate and adaptive immunity synergize to enhance tumor immunotherapy

Academic Article
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Overview

authors

  • Verdeil, G.
  • Marquardt, K.
  • Surh, Charles
  • Sherman, Linda

publication date

  • October 2008

journal

  • Proceedings of the National Academy of Sciences of the United States of America  Journal

abstract

  • Because of mechanisms of self-tolerance, many tumor-specific CD8 T cells exhibit low avidity for tumor antigens and would benefit from strategies that enhance their numbers and effector function. Here we demonstrate that the combined use of two different types of immune adjuvants, one that directly targets the CD8 cell, IL-2/anti-IL-2 mAb complexes, and one that targets the innate immune system, poly(I:C), can achieve this goal. Provision of IL-2/mAb complexes was found to enhance the activation and effector function of low-avidity tumor-specific T cells, yet this was insufficient to achieve tumor eradication. The addition of poly(I:C) further increased the accumulation of granzyme B-expressing effectors within the tumor and resulted in tumor eradication. This strategy presents many of the benefits of whole-body irradiation, including the provision of high levels of homeostatic cytokines, enhanced expansion of effector cells relative to regulatory T cells, and provision of inflammatory cytokines, and is therefore likely to serve as a strategy for both tumor vaccines and adoptive immunotherapy of cancer.

subject areas

  • Adjuvants, Immunologic
  • Animals
  • Antibodies, Monoclonal
  • CD8-Positive T-Lymphocytes
  • Cancer Vaccines
  • Cytokines
  • Immunity
  • Immunotherapy
  • Immunotherapy, Adoptive
  • Interleukin-2
  • Mice
  • Mice, Transgenic
  • Neoplasms
  • Poly I-C
  • Treatment Outcome
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Research

keywords

  • CD8 T cells
  • TLR tumor immunity
  • cytokine complexes
  • interleukin-2
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Identity

PubMed Central ID

  • PMC2575480

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.0805054105

PubMed ID

  • 18936481
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Additional Document Info

start page

  • 16683

end page

  • 16688

volume

  • 105

issue

  • 43

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