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Inhibition of prostate cancer metastasis by administration of a tissue vaccine

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Abstract

Immunotherapy by vaccination represents a novel method for treatment of cancer. In this regard, vaccines with the broadest possible menu of relevant antigens stand the greatest chance of success. Tissue vaccines are composed of material harvested directly from tumors and contain not only antigens associated with neoplastic epithelium, but also those that may be unique to in vivo growth and antigens associated with the tumor stroma. To test the hypothesis that a tissue vaccine, produced by glutaraldehyde fixation of harvested syngeneic prostate tumors (GFT vaccine), could be used for treatment of prostate cancer, male Lobund-Wistar (LW) rats were treated with methylnitrosourea (MNU) and testosterone propionate to induce autochthonous prostate tumors. Tumor-bearing rats were randomly assigned to one of three treatment groups: no treatment (11 rats); vaccination with media (10 rats); or vaccination with the GFT vaccine (19 rats). Vaccination was given initially with Freund’s complete adjuvant and booster doses were given with incomplete Freund’s adjuvant every week until the time of euthanasia. There were no significant differences in mean tumor weight between groups; however, GFT-vaccinated rats had a prolonged survival time; and 4/19 (21%) GFT-vaccinated rats were found to be tumor-free compared to none of the untreated or media-treated controls. Further, pulmonary metastasis occurred in only 5/15 (33%) of GFT-vaccinated rats compared to 10/11 (91%) and 10/10 (100%) of untreated and media-vaccinated controls, respectively. Supernatants of cultured splenocytes from similarly media- and GFT-vaccinated rats demonstrated significant (P < 0.001) increases in IFN-γ and TNF-α from splenocytes of GFT-vaccinated rats, suggesting that GFT vaccination stimulates a Th1 response. In summary, treatment of tumor-bearing rats with a tissue vaccine stimulated a protective immune response that resulted in complete tumor regression in 21% of animals and reduced the number of animals with any evidence of metastasis by nearly 70%. These results suggest that tissue vaccines may be useful for the treatment of prostate cancer.

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Abbreviations

GFT:

Glutaraldehyde-fixed tissue

GM-CSF:

Granulocyte-macrophage colony-stimulating factor

IFN-γ:

Interferon-gamma

LW:

Lobund-Wistar (rat)

MEM:

Modified eagle’s medium

MNU:

Methylnitrosourea

Nu/nu:

Immunodeficient nude mouse

PAIII:

PAIII prostate cancer cell line

PBS:

Phosphate buffered saline

PC346C:

PC346C prostate cancer cell line

PSA:

Prostate specific antigen

PSV:

Prostate-seminal vesicle (complex)

RPMI:

Roswell Park Memorial Institute (media)

TNF-α:

Tumor necrosis factor-alpha

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Authors and Affiliations

  1. Freimann Life Science Center, University of Notre Dame, Notre Dame, IN, 46530, USA

    Mark A. Suckow, William R. Wolter & Valerie T. Sailes

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  1. Mark A. Suckow
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  2. William R. Wolter
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  3. Valerie T. Sailes
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Correspondence to Mark A. Suckow.

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Suckow, M.A., Wolter, W.R. & Sailes, V.T. Inhibition of prostate cancer metastasis by administration of a tissue vaccine. Clin Exp Metastasis 25, 913–918 (2008). https://doi.org/10.1007/s10585-008-9213-z

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  • DOI: https://doi.org/10.1007/s10585-008-9213-z

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