Preclinical testing of a peptide-based, HER2/neu vaccine for prostate cancer

  • Authors:
    • Michael M. Woll
    • Matthew T. Hueman
    • Gayle B. Ryan
    • Constantin G. Ioannides
    • Charles G. Henderson
    • Isabelle A. Sesterhan
    • Shiv Shrivasta
    • David G. McLeod
    • Judd W. Moul
    • George E. Peoples
  • View Affiliations

  • Published online on: December 1, 2004     https://doi.org/10.3892/ijo.25.6.1769
  • Pages:1769-1780
0

Abstract

The HER2/neu protein is over-expressed in multiple epithelial tumors and the source of immunogenic peptides currently under investigation in vaccine trials in ovarian and breast cancers. We sought to define the correlation between HER2/neu expression and risk for prostate cancer recurrence and then determine the potential efficacy of anti-HER2/neu vaccination in prostate cancer patients at risk for recurrence. The risk for prostate-specific antigen (PSA) recurrence in 95 patients undergoing prostatectomy at the Walter Reed Army Medical Center (WRAMC) was calculated and correlated to HER2/neu expression, as determined by immunohistochemical staining. Peripheral blood lymphocytes (PBL) were then isolated from six consecutive human leukocyte antigen (HLA) A2+ patients with HER2/neu+ prostate tumors. These PBL were grown in parallel cultures and stimulated either with no peptide, HER2/neu E75 peptide, or control peptide. The cultures were compared for stimulated proliferation, induced peptide-specific cytotoxicity and tumor-specific cytotoxicity. When assessed by risk group, 69% of the high risk patients' tumors over-expressed HER2/neu compared to 47% of the intermediate risk group (p<0.05). Evaluation of the in vitro immune response of PBL isolated from six consecutive prostate cancer patients revealed a statistically significant increase in E75-stimulated lymphocytic proliferation. E75-stimulated lymphocytes demonstrated an E75-specific cytolytic response in 6/6 prostate cancer patients that increased with successive stimulations. Moreover, these E75-specific lymphocytes also demonstrated tumor-specific lysis against HER2/neu-expressing prostate cancer cell lines. The majority of prostate cancer patients at high risk for recurrence have HER2/neu expressing tumors. Hence, HER2/neu is a viable target for immunotherapeutics such as preventative immunization strategies with HER2/neu peptide vaccines.

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December 2004
Volume 25 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

2016 Impact Factor: 3.079
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APA
Woll, M.M., Hueman, M.T., Ryan, G.B., Ioannides, C.G., Henderson, C.G., Sesterhan, I.A. ... Peoples, G.E. (2004). Preclinical testing of a peptide-based, HER2/neu vaccine for prostate cancer. International Journal of Oncology, 25, 1769-1780. https://doi.org/10.3892/ijo.25.6.1769
MLA
Woll, M. M., Hueman, M. T., Ryan, G. B., Ioannides, C. G., Henderson, C. G., Sesterhan, I. A., Shrivasta, S., McLeod, D. G., Moul, J. W., Peoples, G. E."Preclinical testing of a peptide-based, HER2/neu vaccine for prostate cancer". International Journal of Oncology 25.6 (2004): 1769-1780.
Chicago
Woll, M. M., Hueman, M. T., Ryan, G. B., Ioannides, C. G., Henderson, C. G., Sesterhan, I. A., Shrivasta, S., McLeod, D. G., Moul, J. W., Peoples, G. E."Preclinical testing of a peptide-based, HER2/neu vaccine for prostate cancer". International Journal of Oncology 25, no. 6 (2004): 1769-1780. https://doi.org/10.3892/ijo.25.6.1769