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α-Tocopheryl succinate sensitizes established tumors to vaccination with nonmatured dendritic cells

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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Purpose: Dendritic cells (DCs) are considered potential candidates for cancer immunotherapy due to their ability to process and present antigens to T cells and stimulate immune responses. However, DC-based vaccines have exhibited minimal effectiveness against established tumors in mice and human cancer patients. The use of appropriate adjuvants can enhance the efficacy of DC-based cancer vaccines in treating established tumors. Methods: In this study we have employed α-tocopheryl succinate (α-TOS), a nontoxic esterified analogue of vitamin E, as an adjuvant to enhance the effectiveness of DC vaccines in treating established murine Lewis lung (3LL) carcinomas. Results: We demonstrate that locally or systemically administered α-TOS in combination with nonmatured DCs injected intratumorally (i.t.) or subcutaneously (s.c.) significantly inhibits the growth of preestablished 10-day tumors (mean tumor volume of 77.5 ± 17.8 mm3 on day 30 post–tumor injection) as compared to α-TOS alone (mean tumor volume of 471 ± 68 mm3 on day 30 post–tumor injection). Additionally, the adjuvant effect of α-TOS was superior to that of cyclophosphamide (CTX). The mean tumor volume on day 28 post–tumor injection in mice treated with CTX+DCs was 611 ± 94 mm3 as compared to 105 ± 36 mm3 in mice treated with α-TOS+DCs. Analysis of purified T lymphocytes from mice treated with α-TOS+DC revealed significantly increased secretion of IFN-γ as compared to T cells from the various control groups. Conclusion: This study demonstrates the potential usefulness of α-tocopheryl succinate, an agent nontoxic to normal cell types, as an adjuvant to augment the effectiveness of DC-based vaccines in treating established tumors.

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Fig. 1A–C
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Abbreviations

AO:

acridine orange

CTX:

cyclophosphamide

DC:

dendritic cell

dUTP:

deoxyuridine triphosphate

FACS:

fluorescence-activated cell sorter

FBS:

fetal bovine serum

FITC:

fluorescein isothiocyanate

GM-CSF:

granulocyte-macrophage colony-stimulating factor

IFN-γ:

interferon-gamma

IL-4:

interleukin-4

NaS:

sodium succinate

OCT:

optimal cutting temperature

PBS:

phosphate-buffered saline

PI:

propidium iodide

Tdt:

terminal deoxynucleotidyl transferase

TNF-α:

tumor necrosis factor alpha

α-TOS:

α-tocopheryl succinate

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Acknowledgements

We would like to thank Barbara Carolus for flow cytometric analysis and Meghan Kreeger for technical assistance.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, University of Arizona, 1501 N. Campbell Avenue, Tucson, AZ 85724, USA

    Lalitha V. Ramanathapuram, Claire M. Payne & Emmanuel T. Akporiaye

  2. Molecular and Cell Biology, University of Arizona, Tucson, AZ 85724, USA

    David Bearss

  3. The Arizona Cancer Center, University of Arizona, Tucson, AZ 85724, USA

    David Bearss, Claire M. Payne, Katrina T. Trevor & Emmanuel T. Akporiaye

  4. Center for Vaccines and Immunology, University of Rochester, Rochester, New York, USA

    James J. Kobie

Authors
  1. Lalitha V. Ramanathapuram
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  2. James J. Kobie
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  4. Claire M. Payne
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  5. Katrina T. Trevor
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  6. Emmanuel T. Akporiaye
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Correspondence to Emmanuel T. Akporiaye.

Additional information

Supported by grants 1 RO1 CA94111-02 from the NIH and DAMD 17010126 from the DOD.

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Ramanathapuram, L.V., Kobie, J.J., Bearss, D. et al. α-Tocopheryl succinate sensitizes established tumors to vaccination with nonmatured dendritic cells. Cancer Immunol Immunother 53, 580–588 (2004). https://doi.org/10.1007/s00262-004-0499-7

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  • DOI: https://doi.org/10.1007/s00262-004-0499-7

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