Azuma Koichi, Shichijo Shigeki, Shomura Hiroki, Matsueda Satoko, Fujii Teruhiko, Itoh Kyogo
Department of Immunology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
Breast Cancer Res Treat. 2004 Jul;86(1):19-29. doi: 10.1023/B:BREA.0000032920.95410.63.
HRE2/neu-specific cellular and humoral immune responses are often detected in breast cancer patients, but identification of more immunogenic CTL epitope peptides is necessary prior to development of a cancer vaccine. There is accumulating evidence of strong immunogenicity of peptides capable of inducing both cellular and humoral immune responses. To identify such peptides, this study intended to determine HER2/neu-derived peptides capable of inducing both cellular and humoral immunity in HLA-A24(+) breast cancer patients. IgGs reactive to the HER2(342-350), HER2(485-493), and HER2(553-561) peptides were detected in the sera of these patients with the frequency of 47, 24, and 24%, respectively. These peptides also induced peptide-specific and tumor-reactive CTL activity in the peripheral blood mononuclear cells of HLA-A24(+) breast cancer patients with the frequency of 50, 63, and 25%, respectively, but such activity was not induced from any HLA-A24(-) patients. Cellular and humoral responses to each of these three peptides were also observed in PBMCs and sera from the other epithelial cancer patients. These results may provide a scientific basis for new clinical trials of HER2/neu-peptide-based immunotherapy for breast cancer and also other epithelial cancer patients.
在乳腺癌患者中常常能检测到针对HRE2/neu的细胞免疫和体液免疫反应，但在开发癌症疫苗之前，有必要鉴定出更多具有免疫原性的CTL表位肽。越来越多的证据表明，能够诱导细胞免疫和体液免疫反应的肽具有很强的免疫原性。为了鉴定此类肽，本研究旨在确定能够在HLA - A24(+)乳腺癌患者中诱导细胞免疫和体液免疫的HER2/neu衍生肽。在这些患者的血清中检测到了对HER2(342 - 350)、HER2(485 - 493)和HER2(553 - 561)肽有反应的IgG，其频率分别为47%、24%和24%。这些肽还分别以50%、63%和25%的频率在HLA - A24(+)乳腺癌患者的外周血单核细胞中诱导了肽特异性和肿瘤反应性CTL活性，但在任何HLA - A24(-)患者中均未诱导出这种活性。在其他上皮癌患者的外周血单核细胞和血清中也观察到了对这三种肽中每一种的细胞免疫和体液反应。这些结果可能为基于HER2/neu肽的免疫疗法用于乳腺癌及其他上皮癌患者的新临床试验提供科学依据。
