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Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells.

Publication ,  Journal Article
Dannull, J; Su, Z; Rizzieri, D; Yang, BK; Coleman, D; Yancey, D; Zhang, A; Dahm, P; Chao, N; Gilboa, E; Vieweg, J
Published in: J Clin Invest
December 2005

In this study, we investigated whether elimination of CD4+/CD25+ Tregs using the recombinant IL-2 diphtheria toxin conjugate DAB(389)IL-2 (also known as denileukin diftitox and ONTAK) is capable of enhancing the immunostimulatory efficacy of tumor RNA-transfected DC vaccines. We show that DAB(389)IL-2 is capable of selectively eliminating CD25-expressing Tregs from the PBMCs of cancer patients without inducing toxicity on other cellular subsets with intermediate or low expression of CD25. DAB(389)IL-2-mediated Treg depletion resulted in enhanced stimulation of proliferative and cytotoxic T cell responses in vitro but only when DAB(389)IL-2 was omitted during T cell priming. DAB(389)IL-2 significantly reduced the number of Tregs present in the peripheral blood of metastatic renal cell carcinoma (RCC) patients and abrogated Treg-mediated immunosuppressive activity in vivo. Moreover, DAB(389)IL-2-mediated elimination of Tregs followed by vaccination with RNA-transfected DCs significantly improved the stimulation of tumor-specific T cell responses in RCC patients when compared with vaccination alone. Our findings may have implications in the design of immune-based strategies that may incorporate the Treg depletion strategy to achieve potent antitumor immunity with therapeutic impact.

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Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

December 2005

Volume

115

Issue

12

Start / End Page

3623 / 3633

Location

United States

Related Subject Headings

  • Transfection
  • Time Factors
  • T-Lymphocytes, Regulatory
  • T-Lymphocytes
  • Reverse Transcriptase Polymerase Chain Reaction
  • Receptors, Interleukin-2
  • RNA, Neoplasm
  • RNA
  • Neoplasms
  • Neoplasm Metastasis
 

Citation

APA
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ICMJE
MLA
NLM
Dannull, J., Su, Z., Rizzieri, D., Yang, B. K., Coleman, D., Yancey, D., … Vieweg, J. (2005). Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells. J Clin Invest, 115(12), 3623–3633. https://doi.org/10.1172/JCI25947
Dannull, Jens, Zhen Su, David Rizzieri, Benjamin K. Yang, Doris Coleman, Donna Yancey, Aijing Zhang, et al. “Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells.J Clin Invest 115, no. 12 (December 2005): 3623–33. https://doi.org/10.1172/JCI25947.
Dannull J, Su Z, Rizzieri D, Yang BK, Coleman D, Yancey D, et al. Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells. J Clin Invest. 2005 Dec;115(12):3623–33.
Dannull, Jens, et al. “Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells.J Clin Invest, vol. 115, no. 12, Dec. 2005, pp. 3623–33. Pubmed, doi:10.1172/JCI25947.
Dannull J, Su Z, Rizzieri D, Yang BK, Coleman D, Yancey D, Zhang A, Dahm P, Chao N, Gilboa E, Vieweg J. Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells. J Clin Invest. 2005 Dec;115(12):3623–3633.

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

December 2005

Volume

115

Issue

12

Start / End Page

3623 / 3633

Location

United States

Related Subject Headings

  • Transfection
  • Time Factors
  • T-Lymphocytes, Regulatory
  • T-Lymphocytes
  • Reverse Transcriptase Polymerase Chain Reaction
  • Receptors, Interleukin-2
  • RNA, Neoplasm
  • RNA
  • Neoplasms
  • Neoplasm Metastasis