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Recovery of ζ-chain expression and changes in spontaneous IL-10 production after PSA-based vaccines in patients with prostate cancer

British Journal of Cancer volume 86, pages 168–178 (2002)Cite this article

Abstract

Circulating T lymphocytes of patients with prostate cancer have been reported to have functional deficits, including low or absent ζ-chain expression. To determine whether these functional impairments could be reversed by prostate specific antigen-based vaccination therapy, 10 patients treated with recombinant human prostate specific antigen plus GM-CSF and eight others receiving prostate specific antigen plus oil emulsion in two pilot clinical trials were evaluated prior to and after vaccination for several immunologic end points, including ζ-chain expression and cytokine production by circulating T cells as well as the frequency of T cells able to respond to prostate specific antigen in ELISPOT assays. The flow cytometry assay for ζ-chain expression was standardized to allow for a reliable comparison of pre- vs post-vaccination samples. Prior to therapy, the patients were found to have significantly lower ζ-chain expression in circulating CD3+ cells and a higher percentage of ζ-chain negative CD3+ and CD4+ cells than normal donors. The patients' peripheral blood mononuclear cells spontaneously produced more IL-10 ex vivo than those of normal controls. After vaccination, recovery of ζ-chain expression was observed in 50% of patients in both clinical trials. Also, spontaneous IL-10 secretion by peripheral blood mononuclear cells decreased following immunotherapy in patients treated with prostate specific antigen and GM-CSF. The frequency of prostate specific antigen-reactive T cells was detectable in 7 out of 18 patients vs 4 out of 18 patients prior to vaccination. Only one of 18 patients was a clinical responder. The vaccine had stimulatory effects on the patients' immune system, but post-vaccine immune recovery could not be correlated to progression-free survival in this small cohort of patients with prostate cancer.

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Acknowledgements

Supported in part by the NIH Grants PO-1 DE 12321 (TL Whiteside) and RO1-CA 3513 (TL Whiteside).

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Authors and Affiliations

  1. University of Pittsburgh Cancer Institute, W1041 Biomedical Science Tower, 211 Lothrop Street, Pittsburgh, Pennsylvania, 15213-2582, PA, USA

    N Meidenbauer, W Gooding & T L Whiteside

  2. Department of Pathology, University of Pittsburgh School of Medicine, W1041 Biomedical Science Tower, 211 Lothrop Street, Pittsburgh, Pennsylvania, 15213, PA, USA

    T L Whiteside

  3. Department of Otolaryngology, University of Pittsburgh School of Medicine, W1041 Biomedical Science Tower, 211 Lothrop Street, Pittsburgh, Pennsylvania, 15213, PA, USA

    T L Whiteside

  4. Jenner Biotherapies, Tiberon, California, 94920, CA, USA

    L Spitler

  5. Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, 19107, PA, USA

    D Harris

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Correspondence to T L Whiteside.

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Meidenbauer, N., Gooding, W., Spitler, L. et al. Recovery of ζ-chain expression and changes in spontaneous IL-10 production after PSA-based vaccines in patients with prostate cancer. Br J Cancer 86, 168–178 (2002). https://doi.org/10.1038/sj.bjc.6600039

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