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 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.
Woll
Michael M
MM
Divisions of General Surgery and Urology, Department of Surgery, Walter Reed Army Medical Center, Washington, DC 20307, USA.
Hueman
Matthew T
MT
Ryan
Gayle B
GB
Ioannides
Constantin G
CG
Henderson
Charles G
CG
Sesterhan
Isabelle A
IA
Shrivasta
Shiv
S
McLeod
David G
DG
Moul
Judd W
JW
Peoples
George E
GE
D019496:Cancer Vaccines; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D018734:Genes, erbB-2; D006801:Humans; D007167:Immunotherapy; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000628:therapy*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D012307:Risk Factors
D019496:Cancer Vaccines; D018719:Erb-b2 Receptor Tyrosine Kinases