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

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...

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Bibliographic Details
Published in:	International journal of oncology Vol. 25; no. 6; p. 1769
Main Authors:	Woll, Michael M, Hueman, Matthew T, Ryan, Gayle B, Ioannides, Constantin G, Henderson, Charles G, Sesterhan, Isabelle A, Shrivasta, Shiv, McLeod, David G, Moul, Judd W, Peoples, George E
Format:	Journal Article
Language:	English
Published:	Greece 01-12-2004
Subjects:	Cancer Vaccines Cell Proliferation Gene Expression Profiling Genes, erbB-2 Humans Immunotherapy Male Neoplasm Recurrence, Local - genetics Prostatic Neoplasms - genetics Prostatic Neoplasms - therapy Receptor, ErbB-2 - genetics Risk Factors
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Summary:	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.
ISSN:	1019-6439
DOI:	10.3892/ijo.25.6.1769