1. HER2/neu-derived peptides recognized by both cellular and humoral immune systems in HLA-A2+ cancer patients
Yuki Ishihara, Mamoru Harada, Koichi Azuma, Mayumi Tamura, Hiroki Shomura, Teruhiko Fujii, Kyogo Itoh, Shigeki Shichijo Int J Oncol. 2004 Apr;24(4):967-75.
HER2/neu is one of the most appropriate target antigens for anti-cancer therapy because of its expression in various types of epithelial cancer. HER2/neu can also be a target for both cellular and humoral immune responses. In this study, we attempted to identify HER2/neu-derived peptides, which are able to be recognized by both humoral and cellular immune systems in HLA-A2+ cancer patients. Among 12 HER2/neu-derived peptides having the HLA-A2 binding motifs, immunoglobulin G reactive to each of 7 HER2/neu peptides was detected in the plasma of >50% of cancer patients. Among these 7 peptides, 3 including HER2/neu 444-452, HER2/neu 466-474, and HER2/neu 484-492, effectively induced peptide-specific and HLA-A2-restricted cytotoxic T lymphocyte activity from peripheral blood mononuclear cells of cancer patients, regardless of different HLA-A2 subtypes. Experiments using blocking antibodies and cold inhibition targets revealed that the cytotoxicity against HER2/neu-expressing HLA-A2+ tumor cells was peptide-specific and CD8+ T cell-dependent. Overall, these results indicate that these 3 HER2/neu-derived peptides are efficiently recognized by both the humoral and cellular immune systems, and therefore could be useful for peptide-based immunotherapy for HLA-A2+ patients with various types of epithelial cancer.
2. Immunohistochemical assay of neu/c-erbB-2 oncogene product in paraffin-embedded tissues in early breast cancer: retrospective follow-up study of 245 stage I and II cases
H Battifora, M Gaffey, J Esteban, P Mehta, A Bailey, C Faucett, J Niland Mod Pathol. 1991 Jul;4(4):466-74.
The expression of neu oncoprotein was assayed by immunohistochemistry (IHC) on 245 paraffin-embedded, Stage I and II breast cancers from patients treated at the City of Hope between the years 1980 and 1987. Only cases showing membrane staining were scored as positive. Fifty-four (22%) of the tumors stained positively for neu. Probability of disease-free survival (DFS) and overall survival (OS) was compared based on neu positivity and other prognostic factors. Overall, DFS and OS did not differ significantly among neu-positive and neu-negative cases. However, when only cases with favorable (Stages I and II) nuclear grade were analyzed, OS and DFS were significantly lower in neu-positive cases, with a 9-fold increase in risk of death and a 3-fold increase in risk of relapse. Our findings suggest that immunohistologic study of neu oncoprotein may help to define patients at greater risk among low-stage/low-nuclear-grade patients with breast cancer, a group hitherto recognized as having a good prognosis.
