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Impact of anti-CD25 monoclonal antibody on dendritic cell-tumor fusion vaccine efficacy in a murine melanoma model.

Publication ,  Journal Article
Tan, C; Reddy, V; Dannull, J; Ding, E; Nair, SK; Tyler, DS; Pruitt, SK; Lee, WT
Published in: J Transl Med
June 17, 2013

BACKGROUND: A promising cancer vaccine involves the fusion of tumor cells with dendritic cells (DCs). As such, a broad spectrum of both known and unidentified tumor antigens is presented to the immune system in the context of the potent immunostimulatory capacity of DCs. Murine studies have demonstrated the efficacy of fusion immunotherapy. However the clinical impact of DC/tumor fusion vaccines has been limited, suggesting that the immunosuppresive milieu found in patients with malignancies may blunt the efficacy of cancer vaccination. Thus, novel strategies to enhance fusion vaccine efficacy are needed. Regulatory T cells (Tregs) are known to suppress anti-tumor immunity, and depletion or functional inactivation of these cells improves immunotherapy in both animal models and clinical trials. In this study, we sought to investigate whether functional inactivation of CD4+CD25+FoxP3+ Treg with anti-CD25 monoclonal antibody (mAb) PC61 prior to DC/tumor vaccination would significantly improve immunotherapy in the murine B16 melanoma model. METHODS: Treg blockade was achieved with systemic PC61 administration. This blockage was done in conjunction with DC/tumor fusion vaccine administration to treat established melanoma pulmonary metastases. Enumeration of these metastases was performed and compared between experimental groups using Wilcoxon Rank Sum Test. IFN-gamma ELISPOT assay was performed on splenocytes from treated mice. RESULTS: We demonstrate that treatment of mice with established disease using mAb PC61 and DC/tumor fusion significantly reduced counts of pulmonary metastases compared to treatment with PC61 alone (p=0.002) or treatment with control antibody plus fusion vaccine (p=0.0397). Furthermore, IFN-gamma ELISPOT analyses reveal that the increase in cancer immunity was mediated by anti-tumor specific CD4+ T-helper cells, without concomitant induction of CD8+ cytotoxic T cells. Lastly, our data provide proof of principle that combination treatment with mAb PC61 and systemic IL-12 can lower the dose of IL-12 necessary to obtain maximal therapeutic efficacy. CONCLUSIONS: To our knowledge, this is the first report investigating the effects of anti-CD25 mAb administration on DC/tumor-fusion vaccine efficacy in a murine melanoma model, and our results may aide the design of future clinical trials with enhanced therapeutic impact.

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Published In

J Transl Med

DOI

EISSN

1479-5876

Publication Date

June 17, 2013

Volume

11

Start / End Page

148

Location

England

Related Subject Headings

  • T-Lymphocytes, Regulatory
  • Mice, Inbred C57BL
  • Mice
  • Melanoma
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-12
  • Immunology
  • Humans
  • Forkhead Transcription Factors
  • Female
 

Citation

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Tan, C., Reddy, V., Dannull, J., Ding, E., Nair, S. K., Tyler, D. S., … Lee, W. T. (2013). Impact of anti-CD25 monoclonal antibody on dendritic cell-tumor fusion vaccine efficacy in a murine melanoma model. J Transl Med, 11, 148. https://doi.org/10.1186/1479-5876-11-148
Tan, Chunrui, Varun Reddy, Jens Dannull, Enyu Ding, Smita K. Nair, Douglas S. Tyler, Scott K. Pruitt, and Walter T. Lee. “Impact of anti-CD25 monoclonal antibody on dendritic cell-tumor fusion vaccine efficacy in a murine melanoma model.J Transl Med 11 (June 17, 2013): 148. https://doi.org/10.1186/1479-5876-11-148.
Tan C, Reddy V, Dannull J, Ding E, Nair SK, Tyler DS, et al. Impact of anti-CD25 monoclonal antibody on dendritic cell-tumor fusion vaccine efficacy in a murine melanoma model. J Transl Med. 2013 Jun 17;11:148.
Tan, Chunrui, et al. “Impact of anti-CD25 monoclonal antibody on dendritic cell-tumor fusion vaccine efficacy in a murine melanoma model.J Transl Med, vol. 11, June 2013, p. 148. Pubmed, doi:10.1186/1479-5876-11-148.
Tan C, Reddy V, Dannull J, Ding E, Nair SK, Tyler DS, Pruitt SK, Lee WT. Impact of anti-CD25 monoclonal antibody on dendritic cell-tumor fusion vaccine efficacy in a murine melanoma model. J Transl Med. 2013 Jun 17;11:148.
Journal cover image

Published In

J Transl Med

DOI

EISSN

1479-5876

Publication Date

June 17, 2013

Volume

11

Start / End Page

148

Location

England

Related Subject Headings

  • T-Lymphocytes, Regulatory
  • Mice, Inbred C57BL
  • Mice
  • Melanoma
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-12
  • Immunology
  • Humans
  • Forkhead Transcription Factors
  • Female