HER2/neu-derived peptides recognized by both cellular and humoral immune systems in HLA-A2+ cancer patients

  • Authors:
    • Yuki Ishihara
    • Mamoru Harada
    • Koichi Azuma
    • Mayumi Tamura
    • Hiroki Shomura
    • Teruhiko Fujii
    • Kyogo Itoh
    • Shigeki Shichijo
  • View Affiliations

  • Published online on: April 1, 2004     https://doi.org/10.3892/ijo.24.4.967
  • Pages: 967-975
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Abstract

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.

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April 2004
Volume 24 Issue 4

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

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APA
Ishihara, Y., Harada, M., Azuma, K., Tamura, M., Shomura, H., Fujii, T. ... Shichijo, S. (2004). HER2/neu-derived peptides recognized by both cellular and humoral immune systems in HLA-A2+ cancer patients. International Journal of Oncology, 24, 967-975. https://doi.org/10.3892/ijo.24.4.967
MLA
Ishihara, Y., Harada, M., Azuma, K., Tamura, M., Shomura, H., Fujii, T., Itoh, K., Shichijo, S."HER2/neu-derived peptides recognized by both cellular and humoral immune systems in HLA-A2+ cancer patients". International Journal of Oncology 24.4 (2004): 967-975.
Chicago
Ishihara, Y., Harada, M., Azuma, K., Tamura, M., Shomura, H., Fujii, T., Itoh, K., Shichijo, S."HER2/neu-derived peptides recognized by both cellular and humoral immune systems in HLA-A2+ cancer patients". International Journal of Oncology 24, no. 4 (2004): 967-975. https://doi.org/10.3892/ijo.24.4.967